Social Networks, Stigma, and Hepatitis C Care Among Women Who Inject Drugs: Findings from A Community Recruited Sample.

This study explores the role of perceived HCV stigma and social networks on HCV care among people who inject drugs (PWID) of both sexes, and solely among women who inject drugs (WWID). Data were from 269 HCV positive PWID, community-recruited through street-based outreach in Baltimore, MD. We defined HCV stigma based on participants' perceptions of treatment by others and their need to conceal their HCV status. Among WWID, HCV stigma was linked with decreased odds of undergoing liver disease staging (aOR = 0.33, 95% CI: 0.13,0.85) or to have attempted to get the HCV cure (aOR = 0.39, CI: 0.16,0.97), these associations were not evident in the overall sample with both sexes. Social network characteristics were significant correlates of HCV care in the overall sample, and these associations were stronger among WWID. WWID with more HCV positive social network members had higher odds of an HCV-related healthcare visit in the prior 12 months (aOR = 4.28, CI: 1.29,14.17) and to have undergone liver disease staging (aOR = 2.85, CI: 1.01,8.05). WWID with more social network members aware of the HCV cure were more likely to report an attempt at obtaining the HCV cure (aOR = 5.25, CI: 1.85,14.89). Our results suggest complexity in the role of social networks and stigma on HCV care.

Fluid balance monitoring by cuff-occluded rate of rise of peripheral venous pressure in haemodialysis patients.

Cuff-occluded rate of rise of peripheral venous pressure has been proposed to reflect volume changes in experimental studies. The aim of this study was to evaluate changes in cuff-occluded rate of rise of peripheral venous pressure associated with fluid removal by haemodialysis in six adult patients with chronic renal failure on intermittent haemodialysis. Measurements were carried out before and after each haemodialysis session. The volume of fluid removed (indexed to body surface area) linearly correlated with changes in cuff-occluded rate of rise of peripheral venous pressure (r = 0.84; r(2) = 0.70; p = 0.037). Cuff-occluded rate of rise of peripheral venous pressure may be feasible for future clinical monitoring of individual fluid balance.

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

OBJECTIVE: To determine 'true' glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. MATERIAL AND METHODS: Twenty healthy volunteers (11 females) with a median age of 27 years (range 19-36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. RESULTS: 'True' GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106-129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. CONCLUSIONS: Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Prediction of relative glomerular filtration rate in adults: new improved equations based on Swedish Caucasians and standardized plasma-creatinine assays.

OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma-creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malmö). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malmö equations without (LM) and with LBM-term (LM(LBM)). Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malmö equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.

Contrast Medium-induced Nephropathy. Aspects on Incidence; Consequences; Risk Factors; and Prevention

"Contrast media-induced nephropathy (CIN) is a well-known complication of radiological examinations employing iodine contrast media (I-CM). The rapid development and frequent use of coronary interventions and multi-channel detector computed tomography with concomitant administration of relatively large doses of I-CM has contributed to an increasing number of CIN cases during the last few years. Reduced renal function; especially when caused by diabetic nephropathy or renal arteriosclerosis; in combination with dehydration; congestive heart failure; hypotension; and administration of nephrotoxic drugs are risk factors for the development of CIN. When CM-based examinations cannot be replaced by other techniques in patients at risk of CIN; focus should be directed towards analysis of number and type of risk factors; adequate estimation of GFR; institution of proper preventive measures including hydration and post-procedural observation combined with surveillance of serum creatinine for 1-3 days. For the radiologist; there are several steps to consider in order to minimise the risk for CIN: use of ""low-"" or ""iso-osmolar"" I-CM and dosing the I-CM in relation to GFR and body weight being the most important as well as utilizing radiographic techniques to keep the I-CM dose in gram iodine as low as possible below the numerical value of estimated GFR. There is as yet no pharmacological prevention that has been proven to be effective."

Standardization of p-creatinine assays and use of lean body mass allow improved prediction of calculated glomerular filtration rate in adults: a new equation.

OBJECTIVE: To evaluate the Cockcroft-Gault (CG) equation, using various body weight expressions, and the Sawyer equation in predicting glomerular filtration rate (GFR) using an enzymatic and zero-calibrated Jaffe plasma-creatinine assay, and to derive a new robust equation in adults. MATERIAL AND METHODS: The CG weight measures included total, ideal and adjusted body weight (ABW; lowest of total and ideal) and two lean body mass (LBM) expressions, while the Sawyer equation is based primarily on LBM. Iohexol clearance was used to measure GFR. One derivation set (n = 436; enzymatic assay) was used to evaluate and bias-adjust existing equations when indicated, and to derive a new equation based on plasma-creatinine, age, gender and the body weight measure yielding the best adjusted R2. All equations were then validated in a separate set (n = 414; Jaffe assay). RESULTS: The existing equations all performed similarly in both sets. Prediction errors of equations based on LBM showed no correlation with BMI. The CGABW and Sawyer equations performed best. The new equation with LBM yielded the highest adjusted R2. In the combined set (n = 850), its accuracy (86 %/98 % of estimates within 30 %/50 % of measured GFR) was significantly better than for the CGABW (79 %/95 %) and Sawyer equations (79 %/93 %) (p<0.001) for each 30 mL/min GFR subgroup within +/-30 % and +/-50 %, except within +/-30 % >120 mL/min. Prediction error did not correlate with BMI, age or gender. CONCLUSION: A new creatinine-based equation derived in a mainly Caucasian patient sample is a better predictor of GFR than CG-type equations irrespective of the body weight measure used or, if bias-adjusted, when using zero-calibrated creatinine assays.

A cystatin C-based formula without anthropometric variables estimates glomerular filtration rate better than creatinine clearance using the Cockcroft-Gault formula.

t In 1976, Cockcroft and Gault introduced a widely used formula comprising several anthropometric variables to compensate for the inadequacies of creatinine level as a marker of glomerular filtration rate (GFR). The present work investigates the possibility of introducing cystatin C-based formulas without anthropometric variables to predict GFR, determined by an invasive "gold standard" procedure (iohexol clearance), and to compare the diagnostic efficiency of such formulas with that of Cockcroft and Gault. All 451 adult patients referred to the University Hospital for determination of GFR by iohexol clearance measurements during a period of 6 months were included in the study. Calculations of bias (median percent error), correlation (adjusted R2), and accuracy (percentage of estimates within 30 and 50% of iohexol clearance) were used in the comparison. The cystatin C-based formula GFR (ml/min)=89.12 x cystatin C(-1.675) had lower bias and higher accuracy in predicting GFR than the Cockcroft-Gault formula. If a cystatin C-based formula including gender was constructed: GFR (ml/min)=99.19 x cystatin C(-1.713) x (0.823 for women), an even lower bias and higher accuracy were obtained. It is suggested that measurement of cystatin C should be used for the initial prediction of GFR of a patient.

Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy.

OBJECTIVE: To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age. METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z-scores for (51)Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(-2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores). RESULTS: Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or z-score -0.84 SD), serum cystatin C is significantly more useful. CONCLUSIONS: Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.

A 14-year prospective study of autonomic nerve function in Type 1 diabetic patients: association with nephropathy.

AIMS: Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients. METHODS: Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 micro g/min or > 0.03 g/24 h) and glomerular filtration rate ((51)Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m(2) vs. 11 (9) ml/min/1.72 m(2); P = 0.0074]. CONCLUSION: Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications.

Biliary and total extrarenal clearance of inulin and iohexol in pigs. A source of error when determining gfr as body clearance.

Biliary clearance, total extrarenal clearance, body and renal clearance of inulin and iohexol were determined in 11 normal and 11 nephrectomized pigs. The biliary clearance of inulin, calculated as biliary excretion divided by the plasma concentration, was 0.04 and 0.01 ml min(-1) 10 kg(-1) and of iohexol 0.21 and 0.1 ml min(-1) 10 kg(-1), in normal, respectively, nephrectomized pigs (p < 0.05). The extrarenal clearance of inulin, calculated as body minus renal clearance, was 2.7 and 0.7 ml min(-1) 10 kg(-1) and of iohexol 3.7 and 0.7 ml min(-1) 10 kg(-1) in normal, respectively, nephrectomized pigs (p < 0.05). Some hours after injection of the markers their plasma concentrations were much higher in the nephrectomized pigs. This higher plasma concentration was not matched by an equally higher biliary excretion and therefore biliary clearance decreased. The smaller total extrarenal clearance in nephrectomized pigs, i.e. the overestimation of GFR when calculated as body clearance, indicates that this source of error decreases with decreasing renal function.

Low risk of contrast-medium-induced nephropathy with modern angiographic technique.

OBJECTIVE AND DESIGN: A retrospective study of the incidence of contrast-medium-induced nephropathy (CMN) in patients with renal insufficiency. SUBJECTS: All angiographies with and without endovascular therapeutic procedures (n = 2400) performed at the hospital during 1 year were evaluated. A total of 139 patients were found to have a preangiographic serum-creatinine (s-Cr) of 150 micromol L(-1) or above. Postprocedural serial s-Cr values were present in 118 patients and these were included in the study. RESULTS: Amongst patients receiving only iodinated contrast media (CM) 8% demonstrated a 25% rise in s-Cr. The corresponding figure was 11 and 12.5% amongst patients who were given either iodinated CM together with carbon dioxide (CO2) or CO2 as sole contrast medium. After exclusion of other explanations of impaired renal function all together only seven of 114 patients (6%) were considered to have developed CMN. Four of the seven patients restituted renal function completely, whilst it remained decreased in three. No patient required dialysis. The percentage of diabetic patients were not found to be different in patients with and without signs of CMN. CONCLUSIONS: The present retrospective study indicate that the risk of CMN in connection with angiography is low when modern low-osmolality CM and contrast saving angiographic technique including CO2 is used combined with proper hydration. Patients with diabetes mellitus were not found more frequently in the groups with CMN.

The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses.

Human papillomaviruses (HPV) are epitheliotropic viruses, with some types suggested to be associated with skin cancer. In this study, swab samples collected from five different sites on the skin of renal transplant recipients, dialysis patients, and age- and sex-matched healthy controls were analyzed for HPV DNA by a newly designed PCR test. Most individuals were found to have asymptomatic HPV infections; more specifically, 94% of the renal transplant patients, 82% of the dialysis patients, and 80% of the healthy controls were positive for HPV DNA. The multiplicity of the HPVs detected was astounding: 20 previously described and 30 putatively new types were identified by cloning and sequencing of 33 samples from 13 individuals. These results demonstrate that normal human skin harbors an array of papillomaviruses, most of them previously unknown.

Assessing residual renal function and efficiency of hemodialysis--an application for urographic contrast media.

BACKGROUND: In patients on hemodialysis with end-stage renal disease there is an increasing interest in measuring both residual renal function (RRF) and quantity and quality of dialysis because insufficient dialysis gives higher mortality. For that purpose we have measured clearances of two urographic iodine (I) contrast media (CM) with different molecular masses (iohexol 821 u and iodixanol 1, 550 u). These CM are filtered through glomeruli and dialysis membranes and have higher molecular masses than urea and creatinine and might represent the dialyzability of the hypothetic uremic toxins with a molecular mass of 300-5,000 u. METHODS: Thirteen patients (8 of them were anuric) immediately after hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM injections the iodine concentrations were measured with X-ray fluorescence in blood and, when available, urine during the following 2 days including both the start and end of the next dialysis. Eighteen patients after two dialysis sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample was taken at the start of the next dialysis 2 days later to determine RRF alone. RESULTS: In the 10 anuric patients the extrarenal clearances (mean +/- SD) were 2.5 +/- 1.1 and 2.7 +/- 1.1 ml/min/1.73 m(2) for iohexol and iodixanol, respectively. In patients with RRF good correlations were demonstrated between body clearance, based on two blood samples, and renal clearance of CM. Good correlations (r(2) = 0.853 for iohexol, r(2) = 0.933 for iodixanol) were noted between two-sample and single-sample body clearances. Repeated single sample iohexol clearances gave a coefficient of variation of 15%. During dialysis the clearances of iohexol and iodixanol were, respectively, 69 +/- 16 and 58 +/- 11 ml/min/1.73 m(2) when calculated from a single-pool model (hemodialysis clearance of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45 min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration 45 min after dialysis was used, the clearance values were by 8-10% lower and represented the hemodialysis clearance of CM from the extracellular compartments. The dialysis eliminations of iohexol and iodixanol were similar to that of urea, measured as percentage reduction of serum levels during dialysis. CONCLUSIONS: A single injection of CM at the end of dialysis followed by a single blood sample at the start of the next dialysis gives total body clearance, i.e., an estimation of the RRF. An additional blood sample at the end of the next dialysis gives dialysis efficiency.

Does post-angiographic hemodialysis reduce the risk of contrast-medium nephropathy?

OBJECTIVE: Several strategies have been employed to reduce the incidence of nephrotoxicity in connection with the administration of urographic contrast media. We present the results of a randomized study to explore the effect of a single hemodialysis treatment immediately after an angiographic examination. MATERIAL AND METHODS: The patients studied had moderately reduced renal function. Seventeen of the 32 patients had diabetic nephropathy and 15 had other renal diseases. They were randomly selected to undergo either hemodialysis or standard treatment following the angiographic examination. The glomerular filtration rate (GFR) was determined the day before and 1 week after administration of the contrast medium. All patients were hydrated and received oral calcium-channel blocking treatment before angiography. RESULTS: Hemodialysis lowered the level of contrast medium in plasma by approximately 80%. In spite of this no significant difference in renal iohexol clearance was noted between groups treated and not treated with hemodialysis. CONCLUSIONS: The risk of a marked and sustained reduction in renal function after administration of an iodine contrast medium is low with modern angiographic techniques. Hemodialysis reduces levels of contrast media in plasma but does not reduce the incidence of contrast-medium-induced nephrotoxicity in the GFR range from 10 to 25 ml/min.

Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis. A Swedish multi-center study.

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.

Presence of arteriovenous shunting in transplanted but not in native single kidney in the rat.

OBJECTIVE: We previously reported the presence of renal arteriovenous (A-V) shunting in rats subjected to renal transplant rejection, hydronephrosis and severe hypotension caused by bleeding. The question as to whether blood partially by-passes the renal cortex under certain conditions is still controversial and an alternative explanation for the findings has been vasodilatation. The aim of this investigation was to determine whether A-V shunting is part of the haemodynamic changes taking place after unilateral nephrectomy and if the sympathetic nervous system is involved. MATERIAL AND METHODS: Unilateral nephrectomy was performed and radioactive microspheres (15.5 microm) were injected into the right remaining renal artery 30 min (n = 10), 24 h (n = 13) and 3 weeks (n = 14) later. The proportion of radioactivity in the lungs was considered to reflect A-V shunting in the kidney. Sham-operated animals (n = 30) and animals (n = 10) without previous sham operation, all with two kidneys, were used as controls. Isogenic renal transplantation (n = 10) was performed after bilateral nephrectomy to represent a denervated single kidney status. RESULTS: Renal A-V shunting was significantly (p < 0.001) reduced 30 min and 3 weeks after unilateral nephrectomy compared with controls. In isogenically transplanted rats, A-V shunting was not reduced compared with sham-operated animals, and significantly (p < 0.001) greater compared with the reduced levels of shunting at all times after unilateral nephrectomy. CONCLUSIONS: Reduced renal shunting of microspheres was observed after uninephrectomy and seems to require an intact renal innervation. It is likely that vasodilatation after unilateral nephrectomy and A-V shunting are two separate phenomena.

Pharmacokinetics of glibenclamide and its metabolites in diabetic patients with impaired renal function.

BACKGROUND: Glibenclamide (Gb) may provoke long-lasting hypoglycaemic reactions, and one of the known risk factors is impaired renal function. We have demonstrated Gb to have a terminal elimination half-life of 15 h, and the main metabolites have a hypoglycaemic effect. With few exceptions, detailed studies on second generation sulphonylureas in diabetics with impaired renal function are lacking. Therefore, we analysed the pharmacokinetics of Gb and its active metabolites, 4-trans-hydroxyglibenclamide (M1) and 3-cis-hydroxy-glibenclamide (M2) in this patient group. METHODS: Two groups of 11 diabetic patients with impaired renal function (IRF, iohexol clearance range 7-42 ml.min(-1) . 1.73 m(-2)) or normal renal function (NRF, iohexol clearance range 75-140 ml.min(-1) . 1.73 m(-2)) were compared. A single oral 7-mg dose of Gb was administered after overnight fasting. Serum samples and urine collections were obtained over 48 h and 24 h, respectively. Concentrations of Gb, M1 and M2 were determined by a sensitive and selective high-performance liquid chromatography assay. RESULTS: Peak serum values of M1 (24-85 ng.ml(-1) vs 16-57 ng.ml(-1)), M2 (7-22 ng.ml(-1) vs <5-18 ng.ml(-1)) and M1 + M2 (32-100 ng.ml(-1) vs 23-76 ng.ml(-1)) were higher in the IRF group. AUC and Cmax of Gb were lower and the clearance to bioavailability ratio (CL/f) was higher in the IRF group. AUC and Cmax of M1 were higher and CL/f lower in the IRF group. Much lower amounts of M and M2 were excreted in the urine in the IRF group (7.2% vs 26.4% in 24 h). The fraction of the Gb dose excreted as metabolites (fe(met) 0-24 h), ranged between 0.005 and 0.36 and correlated significantly with renal function measured by iohexol clearance. No other pharmacokinetic differences were found. CONCLUSION: The differences in AUC, Cmax and CL/f of Gb may be explained by a higher free fraction in the IRF group which would increase Gb metabolic clearance. The inverse findings regarding M1 may be explained by the fact that the metabolites are primarily eliminated by the kidneys. After a single dose of Gb, neither Gb, M1 nor M2 seemed to accumulate in diabetic subjects with IRF. As only small amounts of M1 and M2 were excreted in the urine, this indicates one or several complementary non-renal elimination routes, e.g. shunting of metabolised Gb to the biliary excretion route and/or enterohepatic recycling of both metabolites and unmetabolised Gb.

Antidiuretic effect of desmopressin given in hemostatic dosages to healthy volunteers.

The aim of this study was to characterize the magnitude and duration of the antidiuretic effects elicited by desmopressin given in hemostatic dosage intravenously (i.v.) (0.3 microg/kg) or intranasally (i.n.) (300 microg) both as single or repeated doses (four i.n. doses with 12-hr intervals) to healthy volunteers. Urine osmolality increased to a maximum median value of 1,087 mOsmol/kg after the single i.v. dose, 1,065 after the single i.n. dose, and 1,071 during the repeated i.n. dosing schedule, and did not differ significantly between the three dosage schedules. The increase lasted for 24 hr after single doses, and 12 hr after the last of the repeated i.n. doses. Serum sodium did not decrease more than normal diurnal variation after single doses, but decreased marginally below the normal reference range in three volunteers after repeated doses. Lowest median serum sodium concentrations after single i.v. and i.n. doses were 140 and 141 mmol/l, respectively, and 139 after repeated i.n. doses. Body weight changed only marginally after single doses, but increased 1.3 kg during repeated dosing. In adult healthy volunteers, single desmopressin doses give an antidiuretic effect lasting for about 24 hr. There is no difference in magnitude or duration between i.v. or i.n. doses. The effect is prolonged as long as the doses are repeated. Serum sodium is only marginally affected by single doses, but tends to decrease after four repeated doses with 12-hr intervals. If desmopressin is repeated for a period of up to 48 hr, fluid intake should be restricted to 2 liters per day in adults.

Raised platelet levels in diabetes mellitus complicated with nephropathy.

OBJECTIVES: To study if elevated platelet levels are found in early and late diabetic nephropathy. DESIGN: A retrospective study was performed of platelet count in different subgroups of patients with insulin-dependent diabetes mellitus, including patients with long and short duration of diabetes and with early signs of nephropathy. Patients with severe renal failure subjected to renal transplantation were also included. RESULTS: The results suggest that raised platelet levels were associated with early signs of diabetic nephropathy and with female gender. Amongst diabetics progressing to uraemia leading to renal transplant, the platelet level was 50% higher than in non-diabetic uraemic patients. CONCLUSION: It is concluded that raised platelet levels are a common finding in patients with diabetes mellitus complicated by nephropathy.