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Background: Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30–90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. Methods: This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. Results: The median SRF of the right kidney was 49.9% (range: 3–91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0–94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. Conclusions: PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a malignancy with varying clinical outcomes, and monitoring renal function is crucial for patient care. Our study investigates the relationship between renal function and distinct molecular subtypes of prostate adenocarcinomas. We analyzed 72 patients with prostate cancer and chronic kidney disease who underwent radical prostatectomy. We categorized patients based on molecular markers and found that the ERG+/SPINK1+ subgroup had higher postoperative kidney disease stages and serum creatinine levels compared to the ERG+/SPINK1− subgroup, suggesting a connection between SPINK1 overexpression and kidney function. The HOXB13 −/TFF3+ subgroup exhibited higher preoperative serum creatinine levels and kidney disease stages than the HOXB13−/TFF3− subgroup, implying a role for TFF3 in kidney function. Furthermore, our study revealed links between kidney disease stages and prognostic grade groups in different molecular subtypes, highlighting the complex interplay between kidney function and tumor behavior. Our research underscores the importance of considering molecular subtypes in prostate cancer management. Prostate cancer is a prevalent malignancy in male patients, having diverse clinical outcomes. The follow-up of patients diagnosed with prostate cancer involves the evaluation of renal function, because its impairment reduces patient survival rates and adds complexity to their treatment and clinical care. This study aimed to investigate the relationship between renal function parameters and distinctive molecular subtypes of prostate adenocarcinomas, defined by the immunoexpression of the SPINK1, ERG, HOXB13, and TFF3 markers. The study group comprised 72 patients with prostate cancer and associated chronic kidney disease (CKD) who underwent radical prostatectomy. Histopathological, molecular, and renal parameters were analyzed. Patients were categorized based on ERG/SPINK1 and HOXB13/TFF3 status, and correlations with renal function and prognostic grade groups were assessed. The ERG+/SPINK1+ subgroup exhibited significantly higher postoperative CKD stages and serum creatinine levels compared to the ERG+/SPINK1− subgroup. This suggests an intricate relationship between SPINK1 overexpression and renal function dynamics. The HOXB13−/TFF3+ subgroup displayed higher preoperative serum creatinine levels and CKD stages than the HOXB13−/TFF3− subgroup, aligning with TFF3's potential role in renal function. Furthermore, the study revealed associations between CKD stages and prognostic grade groups in different molecular subtypes, pointing out an intricate interplay between renal function and tumor behavior. Although the molecular classification of prostate acinar ADK is not yet implemented, this research underscores the variability of renal function parameters in different molecular subtypes, offering potential insights into patient prognosis. [ABSTRACT FROM AUTHOR]

Introduction Robot-assisted partial nephrectomy (RAPN) is a minimally invasive treatment for localized renal tumours, which can sometimes result in extended warm ischaemic time and serious complications. This study reports on surgical outcomes including feasibility, positive margins, and complications during and after surgery. Material and methods From January 2011 to November 2022, a single centre performed off-clamp sutureless RAPN on 287 patients. The study recorded preoperative patient characteristics, estimated glomerular filtration rate, and tumour features according to the preoperative aspects and dimensions used for an anatomical (PADUA) classification, and utilized the RENAL nephrometry scoring system. Intraoperative details and complications were documented. Postoperative complications within 30 days were classified according to the Clavien-Dindo system. Follow-up appointments were scheduled at 1, 3, and 6 months in the first year, followed by subsequent appointments every 6 months, and then annually. Results The study included 145 males and 142 females, with a mean age of 58.9 years and a mean body mass index of 26.7 kg/m2. The mean PADUA score was 8.3, the average console time was 83 minutes, and the estimated blood loss was 280 mL. The average hospital stay was 3 days, and no intraoperative complications were observed. However, 4 patients (1.4%) experienced post-operative haemorrhage that required laparotomy (Clavien-Dindo stage IIIB), and 4 patients (1.4%) had positive surgical margins. Conclusions Off-clamp selective arterial clamping during minimally invasive partial nephrectomy is a safe and feasible approach for small renal tumours. Further randomized prospective studies are required to confirm if RAPN without clamping offers any renal functional benefits and reduces perioperative bleeding complications. [ABSTRACT FROM AUTHOR]

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Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens. Methods: Patients treated for a CNS tumor were prospectively evaluated up to 12 years after completion of their therapy. Examination of kidney function was performed during routine follow-up visits. Blood pressure and blood and urine parameters were analyzed for kidney function evaluation. Glomerular function was assessed by calculating the estimated glomerular filtration rate (eGFR), tubular functions were analyzed by measuring serum electrolytes, bicarbonate and phosphate reabsorption, and proteinuria was assessed by calculating the protein/creatinine ratio and phosphate reabsorption. Results: None of the 65 patients evaluated suffered from clinically relevant kidney impairment (eGFR < 90 mL/min/L, 73 m2). There was no association between chemotherapy dose and eGFR. Only two patients showed mild signs of tubulopathy and 11 patients were diagnosed with elevated blood pressure. Conclusion: With adequate supportive measures, such as sufficient hydration according to chemotherapy protocol guidelines, as well as avoidance or close monitoring of additional nephrotoxic medication, impaired kidney function is rare in CNS tumor survivors treated with standard chemotherapy. Nonetheless, long-term follow-up is essential for early detection of mild impairment of kidney function. [ABSTRACT FROM AUTHOR]

Objectives: Frailty is a significant public health and clinical issue among the elder population. This study aimed to evaluate the nutritional status and renal function in relation to frailty among elderly Taiwanese. Design: We administered community-based health surveys to the elder population in Chiayi County, Taiwan, from 2017 to 2019. Measurements: We measured nutritional status (including serum albumin and total protein levels), renal function (including serum blood urea nitrogen, creatinine, urine protein, and urine creatinine levels), hand grip strength (GS) and calculated appendicular muscle mass (AMM). Results: The study recruited 3739 participants (2139 women). Participants of both sexes with normal GS had higher serum albumin levels and lower urine protein/creatinine ratios (UPCRs). For the men with normal and weak GS, serum albumin levels were 4.15 ± 0.2 and 4.10 ± 0.2 g/dL (p < 0.01), and UPCRs were 123.1 ± 219.6 and 188.7 ± 366.2 (p < 0.001), respectively. GS was positively correlated with serum albumin and urine creatinine levels (r = 0.136 and 0.177, both p < 0.001). AMM was also positively correlated with serum albumin and urine creatinine levels (r = 0.078 and 0.091, both p < 0.001). In the multivariate regression model, for every 1 g/dL increase in serum albumin level, there was a 1.9 and 1.7-kg increase in GS for men and women (p < 0.05 and p < 0.01), respectively. The final model for predicting GS included age, albumin, BUN, and UPCR (urine creatinine for women) which presented a variance of 22.1% and 13.8%, respectively. Conclusion: Proper dietary nutritional intake and maintaining renal function are key elements for preventing frailty among elder population in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF. Methods: A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF. Results: Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF. Conclusions: In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: This study aimed to verify the effect of 6 months of periodized resistance training (RT) with and without blood flow restriction (BFR) in patients with stage 2 chronic kidney disease (CKD) on glomerular filtration rate (GFR), uremic parameters, cytokines, and klotho–fibroblast growth factor 23 (FGF23) axis. Methods: A total of 105 subjects were randomized in three groups of 35 each: control (CTL), RT, and RT + BFR. A first visit was required for an anamnesis to evaluate the number of medications and anthropometric measurements (body weight, height, and body mass index). Muscle strength (one-repetition maximum) was assessed. Venous blood samples were collected at baseline and after 6 months of training in all patients for the analysis of markers of renal function and integrity, as well as for the determination of the inflammatory profile. Statistical significances were adopted with P < 0.05. Results: Both training therapies attenuated the decline of GFR (P < 0.05). The majority of CTL patients declined to stage 3 CKD (88.5%), whereas fewer incidents were noted with RT (25.7%) and RT + BFR (17.1%). Improved uremic parameters as well as inflammation (IL-6, IL-10, IL-15, IL-17a, IL-18, and TNF-α) and klotho–FGF23 axis in RT and RT + BFR (P < 0.05) were observed. Monocyte chemoattractant protein 1 was not changed (P > 0.05) but presented a large effect size (Cohen's d), demonstrating a propensity for improvement. Conclusion: Six months of periodized RT with and without BFR in patients with stage 2 CKD attenuated the progression of the disease by maintaining GFR, improving uremic parameters, cytokine profile regulation, and klotho–FGF23 axis. [ABSTRACT FROM AUTHOR]

Introduction Unilateral renal function often deteriorates with chronic ureteric obstruction. Our objectives were to determine the change in relative renal function (RRF) by MAG3 renography after intervention for ureteric obstruction, and to identify clinical/epidemiological factors which influence long-term outcomes. Material and methods We identified 228 patients from 2006 to 2017 who underwent MAG3 renography before and after intervention for unilateral ureteric obstruction. Patients were grouped into categories preoperatively - with normal RRF (43-57%) through mild (29-42%), moderate (15-28%) and severe (<15%) impairment of RRF. Patient demographics, types of obstructive uropathy and intervention employed were analysed. Each group was assessed for the absolute change in RRF and change in RRF category postoperatively. Results The mean patient age was 50.4 years (SD 16.7), and 62.3% were female. Overall, the mean preand post-intervention RRF of the obstructed kidney did not differ significantly (32.30% vs. 32.20%, P = 0.835). Most patients remained in their preoperative RRF group: 85.9% of normal, 67.4% of mild, 64.4% of moderate and 73.3% of patients with severe RRF impairment did not change category. Patients with mildly impaired preoperative RRF showed a significant worsening postoperatively (36.37% vs. 34.58%, P = 0.024). The other three groups showed no significant change in RRF following intervention. Multivariate logistic regression analysis showed no statistically significant association between type of intervention, age, gender or diagnosis and improvement in postoperative RRF category. Conclusions Our results show that RRF does not improve significantly after intervention for ureteric obstruction. The aim should therefore be to maintain existing renal function and relieve symptoms. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Dabigatran etexilate has become widely used in New Zealand, but information relating to when renal function monitoring is being undertaken is lacking. AIM: To investigate if clinically appropriate renal function monitoring is being undertaken in New Zealand primary care for stroke prevention in non-valvular atrial fibrillation patients prescribed dabigatran etexilate. METHODS: New Zealand non-valvular atrial fibrillation patients' prescription and primary care health data were extracted from national administrative databases for the period 1 July 2011 to 31 December 2015. The proportion of patients who had serum creatinine measurements at close proximity to treatment initiation and 12-months post initiation were assessed with 95% confidence intervals (CIs) and compared with Fisher's exact test. Log-rank tests for univariate analysis (gender, age, ethnicity and deprivation) effects on serum creatinine testing at dabigatran etexilate treatment initiation and 12-months post initiation were performed. RESULTS: Overall, 1,948 patients who had been dispensed dabigatran etexilate with available primary care health data were identified. A total of 1,752 (89.9% [CI: 88.5–91.2]) patients had a renal function test at dabigatran etexilate initiation. There were 929 (72.8% [CI: 70.2–75.2]) patients who received ≥1 year supply of dabigatran etexilate and of these 207 (22.3% [CI: 19.6.6–25.1]) had a serum creatinine test 1 year after initiation. Demographic univariate analysis yielded insignificant log-rank tests for association with having serum creatinine measurements, except for Pacific Peoples. DISCUSSION: There appears to be sub-optimal adherence to renal function monitoring for non-valvular atrial fibrillation patients who receive more than 12-months' treatment with dabigatran etexilate in New Zealand primary care. [ABSTRACT FROM AUTHOR]

Purpose: Direct acting antiviral agents (DAAs) have greatly improved the clearance of hepatitis C virus (HCV) infection. The effect of DAAs on renal function in post-liver transplant HCV-positive patients remains questionable, especially considering the possibility of drug interactions between immunosuppressants and DAAs. Patients and methods: A retrospective observational study included 84 post-liver transplant patients with HCV infection. Patients were divided into two groups: group I received sofosbuvir plus ribavirin for 24 weeks, group II received sofosbuvir plus daclatasvir for 12 weeks. Laboratory data and eGFR were determined before, at the end, and 6 months after completion of treatment. Results: The treatment was well tolerated with 100% sustained virologic response (SVR 12). There was no statistically significant difference between the two groups regarding clinical and laboratory data before treatment. Mean eGFR significantly reduced from 87.36 mL/min to 76.16 mL/min in group I (P=0.001). However, within 6 months after treatment, mean eGFR recovered to 81.51 mL/min, which was not significant when compared to baseline eGFR (P=0.09). Mean eGFR in group II showed non-significant change. There were no significant changes in immunosuppressive drug levels and eGFR in either group of patients, who received either ciclosporin or tacrolimus before and at the end of treatment. Conclusion: DDAs in post-liver transplant patients with HCV infection were well tolerated and associated with stable renal function. Moreover, sofosbuvir plus daclatasvir regimen showed relatively better renal safety compared to sofosbuvir plus ribavirin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dynamic renal scintigraphy remains the recognized method for evaluation of kidney function and perfusion. Although there is an extensive body of knowledge about the use of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3), much less has been written about renal technetium-99m-ethylenedicysteine (99mTc-EC) scintigraphy. The aim of this study was to determine the normal value of renal function parameters in 99mTc-EC dynamic renal scintigraphy: Tmax and T1/2. The effects of age, left or right side in the retroperitoneal space, and sex on those parameters were examined. MATERIAL AND METHODS: The research was conducted on 123 patients (F/M: 70/53; aged 2-71; averaging 14.8 years of age) with at least one normal kidney. A total of 194 healthy kidneys were examined, including pediatric kidneys. RESULTS: According to this study, the normal value of Tmax is 2.85 min (± 1.16) and T1/2 is 8.7 min (± 3.61). Values calculated for pediatric studies are Tmax is 2.81 (± 1.16) and T1/2 is 8.63 (± 3.71). CONCLUSIONS: The normal value of secretory and excretory renal function parameters was calculated. Although the value is slightly lower for children, this is not statistically significant, as globally there are no differences between the kidney-location sides and sexes for any parameter. [ABSTRACT FROM AUTHOR]

Background: As there are different views on the effects of aminophylline on neonatal renal function, we intended to observe the effects of aminophylline on renal dysfunction in neonates with prenatal asphyxia. Methods: This randomized trial was conducted in the Obstetrics and Gynecology Hospital, Tehran, Iran, from June 2016 to May 2017, in neonates with moderate to severe asphyxia during birth. Fifty-six neonates were divided randomly into two groups. The intervention group received one dose of 5mg/kg slow intravenous aminophylline injection and the placebo group received 2 mL/kg of intravenous 10% solution of dextrose saline during the first hour of life. They were monitored and compared for renal functional indices, electrolytes, and complications of asphyxia during the three days of life. Results: The mean of Cr (37.9 ± 8.8 vs 38.5 ± 9.4 and 20.8 ± 4.8 vs 30.1 ± 5.2 μmol/L), GFR (21.55 ± 4.7 vs 20.25 ± 4.4 and 30.8 ± 7.1 vs 20.1 ± 6.5 mL/minute/1.73 m2), Na (135.1 ± 12.4 vs134.5 ± 11.2 and 128.9 ± 11.5 vs 134.2 ± 10.9 mEq/L), and urine output (98.2 ± 25 vs 96.8 ± 23 and 148.7 ± 35 vs 108.8 ± 20 cc) were in the aminophylline treated and placebo group on the 1st and 3rd days, respectively. The mean difference of Cr (-9.3 (-8.9; -9.7) μmol/L); (P = 0.02), GFR (10.7 (10.1; 11.3) mL/minute/1.73 m2) (P = 0.009), Na (-5.3 (-5.9; -4.7) mEq/L) (P = 0.002), and urine volume (39.9 (24.9; 54.9) cc) (P = 0.001) presented statistically significant differences on the third day between the intervention and placebo group. Conclusion: Aminophylline was effective in preventing renal dysfunction in neonates with asphyxia. Neonates who received aminophylline indicated a significant improvement in GFR and urine output on the first day of life. [ABSTRACT FROM AUTHOR]

Introduction: An accurate assessment of renal function is needed in the majority of clinical settings. Unfortunately, the most used estimated glomerular filtration rate (eGFR) formulas are affected by significant errors in comparison to gold standards methods of measured GFR (mGFR). Objective: The objective of the study is to determine the extent of the error of eGFR formulas compared to the mGFR in different specific clinical settings. Methods: A total retrospectively consecutive cohort of 1,320 patients (pts) enrolled in 2 different European Hospitals (Center 1: 470 pts; Center 2: 850 pts) was collected in order to compare the most common eGFR formulas used by physicians with the most widespread mGFR methods in daily clinical practice (Iohexol Plasma Clearance -Center 1 [mGFR-iox] and Renal Scintigraphy -Center 2 [mGFR-scnt]). The study cohort was composed by urological, oncological, and nephrological pts. The agreement between eGFR and mGFR was evaluated using bias (as median of difference), precision (as interquartile range of difference) accuracy (as P30), and total deviation index. Results: The most accurate eGFR formula in the comparison with gold standard method (Iohexol plasma clearance) in Center 1 was represented by s-creatinine and cystatin C combined Chronic Kidney Disease-Epidemiology Collaboration-cr-cy, even though the P30 is reduced (84%) under the threshold of 60 mL/min/1.73 m2. Similar results were found in Center 2, with a wider discrepancy between mGFR-scnt and eGFR formulas due to the minor accuracy of the nuclear tool in respect to the mGFR-iox. Conclusions: The loss of accuracy observed for the formulas at lower values of GFR suggests the mandatory use of gold standards methods as Iohexol Plasma Clearance to assess the correct status of renal function for critical cases. The center 2 showed lower levels of agreement between mGFR and eGFR suggesting that the errors are partially accounted for the Renal Scintigraphy technique too. In particular, we suggest the use of mGFR-iox in oncological urological and nephrological pts with an eGFR lower than 60 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background: The relationship between renal function and bone mineral density (BMD) is controversial. The aim of this study was to determine the relationship of renal function with BMD and osteoporosis risk in healthy postmenopausal Chinese women. Methods: A cross-sectional study was conducted in 776 healthy postmenopausal Chinese women. Dual-energy X-ray absorptiometry was used to measure BMDs. Clinical, demographic, and biochemical data were obtained at the time of image acquisition. Estimated glomerular filtration rate (eGFR) was calculated using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: Women with eGFR levels of at least 90 ml/min/1.73m2 had a lower prevalence of osteoporosis compared with women with decreased eGFR levels (60 ml/min/1.73 m2 ≤ eGFR < 90.0 ml/min/1.73 m2). BMDs at femoral neck and total hip were significantly lower in the lower eGFR class than the higher class (0.717 ± 0.106 vs 0.744 ± 0.125 g/cm2, P < 0.01; 0.796 ± 0.116 vs 0.823 ± 0.129 g/cm2, P < 0.01, respectively). eGFR was positively correlated with BMDs at femoral neck and total hip in unadjusted analysis (P < 0.05). After controlling for age, menopausal duration and body mass index (BMI), decreased eGFR was not associated with osteoporosis risk. Conclusions: After adjustments for age, menopausal duration and BMI, the decline in renal function was not independently associated with osteoporosis risk in healthy postmenopausal Chinese women. [ABSTRACT FROM AUTHOR]

Background Serum vitamin B-12 is measured to evaluate vitamin B-12 status. Serum methylmalonic acid (MMA) is a specific functional indicator of vitamin B-12 status; however, concentrations increase with impaired renal function. Objective The aim of this study was to describe the distribution of serum vitamin B-12 and MMA in US adults, and estimate age-specific reference intervals for serum MMA in a healthy subpopulation with replete vitamin B-12 status and normal renal function. Methods We examined cross-sectional data for serum vitamin B-12 and MMA in adults participating in the NHANES from 2011 to 2014. Vitamin B-12 was measured by electrochemiluminescence assay and MMA by isotope-dilution liquid chromatography–tandem mass spectrometry. Results In both bivariate and multivariate analyses, age, race/Hispanic origin, and vitamin B-12 supplement use were generally significantly associated with serum vitamin B-12 and MMA concentrations. Serum MMA concentrations increased with age, particularly in persons aged ≥70 y. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations than non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were widest for persons aged ≥70 y compared with younger age groups. Compared with the overall population, the central 95% reference intervals for serum MMA concentrations were considerably narrower for a vitamin B-12–replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, whereas serum MMA showed notable, increases with impaired renal function. Conclusions The higher serum MMA concentrations throughout the entire distribution in older persons (especially persons aged ≥70 y) who are vitamin B-12–replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret vitamin B-12 status in epidemiologic research. [ABSTRACT FROM AUTHOR]

Background Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. Objective To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. Methods We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Results Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease–Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Conclusions Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to examine urine creatinine concentrations in drivers submitted to controlled alcohol abstinence programs. Methods Urine samples (n = 32,210) were screened for ethyl glucuronide (EtG) by immunoassay during a 2-year period. Non-negatives underwent EtG and ethyl sulfate (EtS) confirmation by coupled-column Liquid Chromatography-Tandem Mass Spectrometry. Urine samples were tested for dilution by the analysis of creatinine content with <0.2 g/l indicating a dilute specimen. Results The mean urine creatinine was significantly higher in EtG positives compared to negatives (1.47 ± 0.98 vs. 1.17 ± 0.79 g/l). The difference between positives and negatives was consistent within genders and age groups (<45; ≥45). The higher urinary creatinine in EtG positives is explained by a late antidiuretic effect of alcohol. Conclusion Attempts to dilute urine specimens by drinking water or other liquids before voiding are less effective for EtG/EtS compared with illicit drugs excreted in urine. If the temporary decrease in serum creatinine as a consequence of the late antidiuretic effect of alcohol is confirmed by controlled studies, serum creatinine as an indicator of kidney function should be reconsidered in drinkers. [ABSTRACT FROM AUTHOR]

Segmental ureterectomy (SU) represents a promising alternative for the treatment of upper tract urothelial carcinomas (UTUCs) as it is a less invasive procedure and guarantees the preservation of renal units. The present study evaluated oncological outcomes and renal functions following SU when compared with radical nephroureterectomy (RNU). A total of 26 patients with UTUCs who underwent SU (n=12) or RNU (n=14) were retrospectively evaluated. SU was performed in patients with clinically unifocal disease. In the SU group, the following surgeries were carried out: 7 direct ureterocystoneostomy, 1 reimplantation on psoas hitch bladder, 1 reimplantation on Boari flap bladder, 2 ureteral end-to-end anastomosis and 1 subtotal ureterectomy. In the SU group, tumors were low grade urothelial carcinoma (UC) in 6 patients, high grade UC in 5 patients and high grade UC with squamous cell differentiation in 1 patient, as well as ≤pT1 in 5, ≥pT2 in 6 and pTis in 1 patient; 'p' refers to the pathological state. The 5-year overall, cancer-specific, recurrence free and metastasis free survival in the SU group were 77.8, 87.5, 34.4 and 80.8%, respectively, which all exhibited no significant differences when compared with those of the RNU group. With regard to renal function, postoperative estimated glomerular filtration rates were preserved in the SU group. The present study demonstrated that SU does not result in poorer cancer control when compared with RNU. Thus, SU is an acceptable alternative to RNU in selected cases, as it is less invasive and preserves renal functions. [ABSTRACT FROM AUTHOR]

Background Renal function can be estimated with formulas, which are inaccurate, or measured with gold standard methods, which are reliable but unpractical. We propose to simplify the plasma clearance of iohexol, a gold standard method to measure renal function, by dried blood spot (DBS) testing. Methods We compared glomerular filtration rate (GFR) values assessed by DBS and the reference plasma analysis technique. We tested in vitro the agreement between non-volumetric and volumetric DBS with the reference technique. Then, we performed a clinical validation in vivo between volumetric DBS and plasma analysis in 203 patients. The agreement was evaluated with the concordance correlation coefficient (CCC), the total deviation index (TDI) and the coverage probability. We defined acceptable agreement as a TDI <10%. Results In the in vitro studies, the non-volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric method showed better but insufficient agreement, TDI = 13.0%, with the reference method in plasma. The non-volumetric DBS was rejected. To improve the agreement of the volumetric DBS, iopamidol was used as an internal standard. This method showed acceptable agreement, TDI = 9.0% with the analysis in plasma, and was selected as the definitive DBS method. In the in vivo studies, the agreement between the final DBS method and the reference technique was acceptable: TDI = 9.5%. This indicates that 90% of the GFR values ranged from −9.5% to + 9.5% compared with the reference method. Conclusions We simplified the plasma clearance of iohexol using DBS without losing accuracy and precision with respect to the reference technique. This may facilitate the use of a reliable determination of renal function to the medical community. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to evaluate the correlation between renal function and heart function/echocardiographic parameters and epicardial adipose tissue thickness (EATT), respectively. Material and methods: Fifty patients with type 2 diabetes (T2D) were included in this study. Several laboratory parameters were obtained (HbA1c, fasting blood glucose, LDL-cholesterol, creatinine) and eGFR was calculated. Anthropometric measurements were performed (weight, waist and hip circumferences, 4 skinfolds, based on which % body fat was calculated). Patients underwent echocardiographic assessment to evaluate structural and functional parameters, including EATT. Left ventricular mass (LVM) was calculated and the geometric changes of the left ventricle were evaluated. Results: Forty-six per cent of the patients had a LV ejection fraction (EF) <55% and 34% had diastolic dysfunction. There were no significant differences between the three eGFR groups with regards to metabolic parameters, but LVEF was lower (53.0 × 0.8%, 54.4 × 2.4%, and 55.2 × 1.5%, respectively) and EATT was higher (11.0 × 1.0 mm, 8.58 × 2.2 mm, and 7.63 × 2.6 mm, respectively) with a lower eGFR (p = 0.04). More patients with eGFR <90 mL/min/1.73 m² had cardiac hypertrophy compared with those with eGFR ≥90 mL/min/1.73 m² (p = 0.04). EATT correlated positively with several anthropometric parameters, e.g. weight (r = 0.309, 95% CI: 0.022 to 0.549, p = 0.03), BMI (r = 0.398, 95% CI: 0.123 to 0.616, p = 0.004), and negatively with LVEF (r = -0.496, 95% CI: -0.687 to -0.242, p = 0.0003) and eGFR (r = -0.293, 95% CI: -0.531 to -0.013, p = 0.04). In patients with LVEF <55% vs. ≥55%, the EATT was significantly higher (9.5 × 1.99 mm vs. 7.33 × 2.37 mm, p = 0.013). Conclusion: In patients with T2D decreased renal function was associated with lower LVEF and higher EATT. EATT was also higher in patients with reduced LVEF. [ABSTRACT FROM AUTHOR]

ALDH16A1 is a novel member of the ALDH superfamily that is enzymatically-inactive and highly expressed in the kidney. Recent studies identified an association between a rare missense single nucleotide variant (SNV) in the ALDH16A1 gene and elevated serum uric acid levels and gout. The present study explores the mechanisms by which ALDH16A1 influences uric acid homeostasis in the kidney. We generated and validated a mouse line with global disruption of the Aldh16a1 gene through gene targeting and performed RNA-seq analyses in the kidney of wild-type (WT) and Aldh16a1 knockout (KO) mice, along with plasma metabolomics. We found that ALDH16A1 is expressed in proximal and distal convoluted tubule cells in the cortex of the kidney and in zone 3 hepatocytes. RNA-seq and gene ontology enrichment analyses showed that cellular lipid and lipid metabolic processes are up-regulated. Three transporters localized in the apical membrane of the proximal convoluted tubule of the kidney known to influence urate/uric acid homeostasis were found to be up-regulated ( Abcc4 , Slc16a9 ) or down-regulated ( Slc17a3 ). An initial metabolomics analysis in plasma revealed an altered lipid profile in KO mice that is in agreement with our RNA-seq analysis. This is the first study demonstrating a functional role of ALDH16A1 in the kidney. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that diet and renal function are related. Little is known, however, about the association of consumption of whole grains, fruit and vegetables with urinary albumin:creatinine ratio (ACR) and changes in estimated glomerular filtration rate (eGFR). We investigated this in a population-based cohort aged 26-65 years. Data were from 3787 participants from the Doetinchem cohort study, who were examined ≥3 times, 5 years apart. Consumption of food groups was assessed at each round with a validated FFQ. GFR was estimated at each round from routinely measured cystatin C and creatinine using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. ACR was measured at the last round. Generalised estimated equation models were performed to examine associations with changes in eGFR. Linear regression was used to examine associations with ACR. Adjustments were made for covariates related to lifestyle, biological factors and diet. Mean baseline eGFR was 104;⋅5 (SD 13;⋅7) and mean annual declinewas -0;⋅95 (SD 0;⋅67) ml/min per 1;⋅73m² over a 15-year follow-up. A trend was observed towards slightly less annual decline in eGFR among those with higher consumption of whole grains (P=0;⋅06). This association, however, was attenuated and no longer significant in multivariate models (P=0;⋅29). Consumption of fruit and vegetables was not associated with changes in eGFR and urinary ACR. In conclusion, consumption of whole grains, fruit and vegetables is not associated with changes in eGFR and mean ACR. As this was the first longitudinal study into this association in the general population, and as results are only partially in line with related studies, further research is recommended. [ABSTRACT FROM AUTHOR]

Background: Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction.Methods: Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery.Results: There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition.Conclusions: The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction. [ABSTRACT FROM AUTHOR]

Transplant recipients are prone to viral infections, which could affect renal transplantation outcome. Our aim was to assess the effects of early human cytomegalovirus ( CMV) DNAemia on transplant renal function. A total of 264 (age 50.9 ± 13.5; male 55%) renal transplantation recipients undergoing preemptive anti- CMV therapy were retrospectively categorized based on early (<3 months post-Tx) CMV peak viral load ( PVL); PVL ≤ 536, PVL536-6310, or PVL > 6310 International Units/ml ( IU/ml). Estimated glomerular filtration rate ( eGFR) was analyzed between 1 and 36 months post-transplantation with Kruskal-Wallis test, linear regression, and a linear mixed-effects model. CMV infection was detectable in 113 (43%) recipients within 49 [38-67] days. Subjects with PVL > 6310 had statistically significant ~5-13 ml/min lower eGFR between 3 and 36 months compared to PVL ≤ 536 and PVL536-6310. eGFR declined from 46.1 to 40.7 ml/min/1.73 m2 (−12%) over 3 years, and the annual decrease for pronounced infection with high PVL was 2.0 ml/min/1.73 m2 faster than for noninfected or mildly infected subjects. In conclusion, high CMV DNAemia early after renal transplantation was associated with significant loss of renal function, from which subjects did not recover. The severity of infection (high PVL early post-transplantation), more than the infection per se, was related to irreversible and progressive loss of renal function. [ABSTRACT FROM AUTHOR]

Background: The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function.Methods: Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m2 were used as outcome.Results: eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively.Conclusions: In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics). [ABSTRACT FROM AUTHOR]

Background: Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. Methods: We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounderswere used to study the association between OPG and eGFR. Analyseswere stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. Results: In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73m2) eGFR increased by 0.35 mL/min/1.73m2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73m2), eGFR decreased by 1.54 (95% CI - 2.06 to - 1.01) per 1 SD increase in serum OPG. Conclusions: OPGwas associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function. [ABSTRACT FROM AUTHOR]

Background: The change of estimated glomerular filtration rate (eGFR) with off-treatment nucleos(t)ide analogues (NA) in chronic hepatitis B patients (CHB) is unclear. This study is aimed to evaluate the off-treatment eGFR after 3 years of therapy with telbivudine (LdT) or entecavir (ETV) and to assess predictive factors for eGFR improvement.Methods: From January 2009 to December 2011, we identified NA-naïve patients who were at least 20 years of age diagnosed with compensated CHB. All patients received a 3-year NA treatment and 1 year off-treatment follow-up; the initial selection of patients for LdT or ETV treatment was at the physicians' discretion. An increase of more than 10% in eGFR from the baseline was identified as an improvement. The change of chronic kidney disease stages were recorded and compared with baseline at year 3 and year 4, respectively.Results: This study included two groups consisting of 46 patients each (each with3 years of treatment with LdT or ETV). In LdT-treated patients, the mean eGFR increased from 94.3 ± 28.3 to 104.0 ± 31.2 mL/min/1.73 m2 in year 3 (p = 0.01) and from 104.0 ± 31.2 to 104.0 ± 28.8 mL/min/1.73 m2 in year 4 (p = 0.99). However, in ETV-treated patients, the mean eGFR decreased from 93.1 ± 26.1 to 85.5 ± 25.1 mL/min/1.73 m2 in year 3 (p = 0.0009) and from 85.5 ± 25.1 to 87.7 ± 24.8 mL/min/1.73 m2 in year 4 (p = 0.2). After a multivariate analysis, the predictors for the off-treatment eGFR improvement were the LdT treatment (odds ratio [OR], 3.97 (1.37-11.5), p = 0.01) and pre-treated eGFR (OR, 0.98 (0.95-1.00), p = 0.04).Conclusions: At year 4, 48.8 and 21.3% patients had an improved eGFR from baseline in LdT and ETV patients, respectively. Telbivudine may have a protective renal effect that can last for one year after treatment in non-cirrhotic CHB patients without a virological breakthrough. [ABSTRACT FROM AUTHOR]

Background/Objective: High protein oral nutritional supplements (ONS) are regularly prescribed to undernourished patients; however usage of these in older adults is being discussed, as their renal function might have declined with age. Therefore, the aim of the current study was to evaluate the effects of 8 week long consumption of high protein ONS on the renal function of nursing home residents in need of supplementation. Furthermore, within the same setup, differences in gastro-intestinal tolerance between a standard and a more concentrated version of an ONS were investigated. Design: Randomized, controlled, single-blind, parallel-group, multi-country trial (NTR2565). Setting: Nursing home. Participants: 67 nursing home residents in need of ONS (energy-dense, small volume group n=32; standard volume group n=35). Intervention: Protein supplementation was provided by either a standard (200ml, 300kcal, 20g protein) or an energy-dense, small volume (125ml, 300kcal, 18g protein) ONS during the 8 week long study. Measurements: Primary outcome was gastro-intestinal tolerance, assessed by daily stool frequency and consistency, and occurrence and intensity of self-reported gastrointestinal symptoms. Safety was measured via the occurrence of (serious) adverse events, vital signs, as well as liver-and kidney function monitoring. Results: No clinically relevant and, except for flatulence, no statistically significant differences in gastro-intestinal tolerance were observed between groups. No significant difference between groups was found for estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio at baseline and week 8, nor for the changes from baseline. Adverse events and the changes in monitored renal parameters over the study period did not point to a deterioration of renal function. Conclusion: High protein ONS seems to be well-tolerated and safe; there is no indication that it affects renal function in nursing home residents, including patients with stage 3 chronic kidney disease, under the conditions tested. Results did not suggest a difference in the effect on renal function between standard and energy-dense small volume ONS format. [ABSTRACT FROM AUTHOR]

We aimed to clarify the effect of low-carbohydrate diet (LCD) on renal function in overweight and obese individuals without chronic kidney disease (CKD). Literature searches were performed using EMBASE, MEDLINE and Cochrane Library until December 2015. We selected articles that reported human studies from their inception until December 2015 in English using the following searching terms: ‘Low carbohydrate diet’ AND (‘Clinical trial’ OR ‘Clinical study’ OR ‘Clinical investigation’ OR ‘Observational study’ OR ‘Cohort study’). We compared the effects of LCD on renal function, defined as change in estimated glomerular filtration rate (eGFR), assessed in randomised-controlled trials. We calculated the mean change in eGFR and the mean change in standard deviations by eGFR or creatinine clearance, and compared the mean change in eGFR and standard deviations in LCD with those in the control diet using fixed-effects models. We selected nine randomised controlled trials including 1687 participants (861 were fed LCD and 826 were fed the control diet). The mean change in eGFR in the LCD group was −4·7 to 24·0 ml/min per 1·73 m2 and that in the control diet group was −4·1 to 10·8 ml/min per 1·73 m2. The mean change in eGFR in the LCD group was greater than that in the control diet (0·13 ml/min per 1·73 m2; 95 % CI 0·00, 0·26). In the present meta-analysis, we identified that the increase in eGFR was greater in LCD compared with the control diet in overweight and obese individuals without CKD. [ABSTRACT FROM PUBLISHER]

The influence of sleep restriction ( SR) during pregnancy on blood pressure and renal function among female adult offspring was investigated. Pregnant Wistar rats were distributed into control and SR groups. The SR was performed between the 14th and 20th days of pregnancy (multiple platforms method for 20 h/day). At 2 months of age, half of the offspring from both groups were subjected to an ovariectomy (ovx), and the other half underwent sham surgery. The groups were as follows: control sham (Csham), control ovx (Covx), SR sham ( SRsham), and SR ovx ( SRovx). Renal function markers and systolic blood pressure ( BPi, indirect method) were evaluated at 4, 6, and 8 months. Subsequently, the rats were euthanized, kidneys were removed, and processed for morphological analyses of glomerular area ( GA), number of glomeruli per mm3 ( NG), and kidney mass ( KM). Increased BPi was observed in the Covx, SRsham, and SRovx groups compared to Csham at all ages. Increased plasma creatinine concentration and decreased creatinine clearance were observed in the SRsham and SRovx groups compared to the Csham and Covx groups. The SRovx group showed higher BPi and reduced creatinine clearance compared to all other groups. The SRovx group showed reduced values of GA and KM, as well as increased NG, macrophage infiltration, collagen deposit, and ACE1 expression at the renal cortex. Therefore, SR during pregnancy might be an additional risk factor for developing renal dysfunction and increasing BP in female adult offspring. The absence of female hormones exacerbates the changes caused by SR. [ABSTRACT FROM AUTHOR]

Background: S-1 is an oral anticancer drug, containing tegafur (a prodrug of 5-fluorouracil, 5-FU), 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. As renal dysfunction is known to increase exposure of 5-FU following S-1 administration, the incidence of severe adverse reactions is increased in patients with impaired renal function. However, no reliable information on its dose modification for patients with renal dysfunction has been provided. Methods: We conducted a prospective pharmacokinetic study to develop an S-1 dosage formula based on renal function. Sixteen cancer patients with various degrees of renal function received a single dose of S-1 at 40 mg/m. A series of blood samples were collected at predefined times within 24 h to assess the plasma concentration profiles of 5-FU, 5-chloro-2,4-dihydroxypyridine, and tegafur. A mathematical model for the relationship between renal function and exposure of 5-FU was constructed by a population pharmacokinetic analysis. Results: The clearance of 5-FU following S-1 administration was related to body surface area and creatinine clearance in the range 15.9-108.8 mL/min as estimated by the Cockcroft-Gault equation. The S-1 dosage formula was derived as follows:where AUC is the area under the concentration-time curve, CLcr is creatinine clearance, and BSA is body surface area. The recommended daily doses of S-1 in Asia and Europe were also proposed as nomograms according to exposure matching to the previously reported area under the concentration-time curve of 5-FU, which confirmed the efficacy and toxicity in pivotal registration studies. Conclusions: We have developed a novel formula for determining the S-1 dosage on the basis of renal function. Further validation is needed to confirm the formula for practical application. [ABSTRACT FROM AUTHOR]

Aim: We aimed to study the relationships of loop diuretic dose with renal function and clinical outcomes in patients with chronic heart failure (HF).Methods and Results: Loop diuretic dose at baseline was recorded in patients included in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). The relationship to change in estimated glomerular filtration rate (eGFR) over time and to the first occurrence of the composite outcome of cardiovascular (CV) death or hospitalization owing to HF was examined in propensity score matched cohorts. Of the 5011 patients, 2550, 745, and 449 were receiving >80 mg (high), 41-80 mg (medium) and ≤40 mg (low) of loop diuretics in furosemide equivalent daily dosages, respectively, which were used to assemble 229, 385, and 1045 pairs of propensity-matched high, medium, and low dose cohorts. Compared with matched no loop diuretic groups, eGFR declined 0.3 ± 0.2, 0.3 ± 0.3 and 1.2 ± 0.5 mL/min/1.73 m(2) /year in the low-, medium-, and high-dose groups, respectively. Compared with matched no loop diuretic groups, hazard ratios (HR) (95% confidence intervals) for outcome associated with low-, medium- and high-dose groups were 1.71 (1.41-2.06), 1.99 (1.50-2.64), and 2.94 (1.95-4.41), respectively. Higher loop diuretic dose was particularly associated with increased risk for hospitalization owing to HF: HR 4.80 (2.75-8.37), P < 0.001.Conclusions: The use of loop diuretics was associated with a slightly greater rate of decline in eGFR, which did not vary significantly by diuretic dose.Loop diuretic dose was associated with higher risks of (CV) mortality and predominantly hospitalization owing to HF, which appeared to be higher among those receiving higher daily doses. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients.Method/design: ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3-8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3-8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy.Discussion: As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact.Trial Registration: Clinicaltrials.gov: NCT01843348, date of registration--18 April 2013; EUDRACT number: 2011-005238-21, date of registration--20 March 2012. [ABSTRACT FROM AUTHOR]

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. [ABSTRACT FROM AUTHOR]

Background: As the average age of the HIV-positive population increases, there is increasing need to monitor patients for the development of comorbidities as well as for drug toxicities.Methods: We examined factors associated with the frequency of measurement of liver enzymes, renal function tests, and lipid levels among participants of the Canadian Observational Cohort (CANOC) collaboration which follows people who initiated HIV antiretroviral therapy in 2000 or later. We used zero-inflated negative binomial regression models to examine the associations of demographic and clinical characteristics with the rates of measurement during follow-up. Generalized estimating equations with a logit link were used to examine factors associated with gaps of 12 months or more between measurements.Results: Electronic laboratory data were available for 3940 of 7718 CANOC participants. The median duration of electronic follow-up was 3.5 years. The median (interquartile) rates of tests per year were 2.76 (1.60, 3.73), 2.55 (1.44, 3.38) and 1.42 (0.50, 2.52) for liver, renal and lipid parameters, respectively. In multivariable zero-inflated negative binomial regression models, individuals infected through injection drug use (IDU) were significantly less likely to have any measurements. Among participants with at least one measurement, rates of measurement of liver, renal and lipid tests were significantly lower for younger individuals and Aboriginal Peoples. Hepatitis C co-infected individuals with a history of IDU had lower rates of measurement and were at greater risk of having 12 month gaps between measurements.Conclusions: Hepatitis C co-infected participants infected through IDU were at increased risk of gaps in testing, despite publicly funded health care and increased risk of comorbid conditions. This should be taken into consideration in analyses examining factors associated with outcomes based on laboratory parameters. [ABSTRACT FROM AUTHOR]

Proper control of the cell cycle is mandatory during homeostasis and disease. The balance of p53 and MDM2 integrates numerous signalling pathways to regulate the cell cycle, which is executed by multiple proteins including the cyclins, cyclin kinases and cyclin kinase inhibitors. Mutations or environmental factors that affect cell cycle control can lead to inappropriate hyperplasia or cancer as well as to cell loss and tissue atrophy. Normal kidney function is maintained largely by post-mitotic quiescent cells in the G0 phase with a low turnover. Early cell cycle activation during kidney injury contributes to cell death via mitotic catastrophe, i.e. death via mitosis, e.g. of cell with significant DNA damage. At later stages, cell cycle entry supports tissue regeneration and functional reconstitution via cell hypertrophy and/or cell proliferation. It is of note that so-called proliferation markers such as Ki67, PCNA or BrdU identify only cell cycle entry without telling whether this results in cell hypertrophy, cell division or mitotic catastrophe. With this in mind, some established concepts on kidney injury and regeneration are to be re-evaluated. Here, we discuss the components and functional roles of p53/MDM2-mediated cell cycle regulation in kidney homeostasis and disease. [ABSTRACT FROM AUTHOR]

Background: the impact of renal function and its changes and the occurrence of cardiovascular events on changes in N-terminal pro-brain natriuretic peptide levels (NT-proBNP) is unknown in very old age. Objective: to assess whether increase in NT-proBNP levels over time is still associated with cardiac disease and mortality in very old age, independent of renal function. Methods: changes in NT-proBNP levels between age 85 and 90 years and their associations with incident cardiac disease, (cardiovascular) mortality and renal function were assessed in 252 nonagenarian participants from a population-based sample of the Leiden 85-plus Study. Results: median NT-proBNP increase over 5 years was 154 pg/ml (inter-quartile range: 29-549), while in the same period estimated glomerular filtration rate (eGFR) decreased by 5.8 ml/min/1.73 m2 (standard deviation 7.5). Participants with increasing NT-proBNP levels more frequently developed heart failure and atrial fibrillation (odds ratio 2.79, 95% confidence interval (CI) 1.11-7.02 and 2.63, 95% CI 1.02-6.79, respectively, adjusted for eGFR at age 85 and change in eGFR) between age 85 and 90 years. Increasing NT-proBNP levels between age 85 and 90 years were associated with an increased cardiovascular mortality risk after age 90 years compared with not-increasing NT-proBNP levels (hazard ratio 1.62, 95% CI 1.04-2.51, adjusted for eGFR at age 90 years and change in eGFR). Conclusion: in the oldest old, increase in NT-proBNP is associated with incident heart failure and atrial fibrillation and risk for cardiovascular mortality, independent of decreasing renal function. [ABSTRACT FROM AUTHOR]

Background Vitamin K–dependent factors protect against vascular and renovascular calcification, and vitamin K antagonists may be associated with a decreased glomerular filtration rate (GFR). Objectives This study analyzed changes in GFR during long-term treatment with warfarin or dabigatran etexilate (DE) in patients enrolled in the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial. Methods Of the 18,113 patients in the RE-LY study randomized to receive DE (110 mg or 150 mg twice daily) or warfarin, 16,490 patients with atrial fibrillation had creatinine values measured at baseline and at least 1 follow-up visit. Changes in GFR for up to 30 months were evaluated. Results GFR declined in all treatment groups. After an average of 30 months, the mean ± SE decline in GFR was significantly greater with warfarin (–3.68 ± 0.24 ml/min) compared with DE 110 mg (–2.57 ± 0.24 ml/min; p = 0.0009 vs. warfarin) and DE 150 mg (–2.46 ± 0.23 ml/min; p = 0.0002 vs. warfarin). A decrease in GFR >25% was less likely with DE 110 mg (hazard ratio: 0.81 [95% confidence interval: 0.69 to 0.96]; p = 0.017) or DE 150 mg (hazard ratio: 0.79 [95% confidence interval: 0.68 to 0.93]; p = 0.0056) than with warfarin in the observation period >18 months. Patients with poor international normalized ratio control (i.e., time in therapeutic range <65%) exhibited a faster decline in GFR. A more pronounced decline in GFR was associated with previous warfarin use and with the presence of diabetes. Conclusions Patients with atrial fibrillation receiving oral anticoagulation exhibited a decline in renal function that was greater in those taking warfarin versus DE, and it was amplified by diabetes and previous vitamin K antagonist use. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600 ) [ABSTRACT FROM AUTHOR]

The drugs used in chemotherapy treatments have little specificity, attack tumor cells, and also injure proliferative tissues. Knowledge of the functions of micronutrients has greatly increased, especially of Selenium (Se) that presents immunomodulatory and antitumor functions. The present study evaluated the health-related quality of life of patients undergoing chemotherapy for the treatment of leukemias and lymphomas (LL) and solid tumors (ST) while receiving Selenium (Se) supplementation. This is a randomized, double-blind, crossover study that evaluated the quality of life (EORTC-QLQ-C30 questionnaire), renal and liver functions of patients supplemented with Se. There was no statistically significant alteration in LL patients. However, the fatigue and nausea scores after 30 days did decrease in this group as well as in the ST group. After 1 year supplementation with Selenium, a more noticeable decrease in the scores concerning fatigue and nausea could be observed in the ST group, when compared with the beginning of the study. The LL patients also presented a decrease in the fatigue scores and physical functions. The kidney function as well as liver function has improved after Selenium supplementation when compared with the placebo intake in LL and ST patients, more remarkably in the LL group. Supplementation with Selenium promotes the reduction of chemotherapy side effects in cancer patients, especially by improving the conditions of patients with fatigue, nausea, and impaired physical function. Renal and liver functions have also improved. [ABSTRACT FROM AUTHOR]

Background We investigate whether the urinary proteome refines the diagnosis of renal dysfunction, which affects over 10% of the adult population. Methods We measured serum creatinine, estimated glomerular filtration rate (eGFR) and 24-h albuminuria in 797 people randomly recruited from a population. We applied capillary electrophoresis coupled with mass spectrometry to measure multi-dimensional urinary proteomic classifiers developed for renal dysfunction (CKD273) or left ventricular dysfunction (HF1 and HF2). Renal function was followed up in 621 participants and the incidence of cardiovascular events in the whole study population. Results In multivariable-adjusted cross-sectional analyses, higher biomarker levels analysed separately or combined by principal component analysis into a single factor (SF), correlated (P ≤ 0.010) with worse renal function. Over 4.8 years, higher HF1 and SF predicted (P ≤ 0.014) lowering of eGFR; higher HF2 predicted (P ≤ 0.049) increase in serum creatinine and decrease eGFR. HF1, HF2 and SF predicted progression from CKD Stages 2 or ≤2 to Stage ≥3, with risk estimates for a 1-SD increment in the urinary biomarkers ranging from 38 to 71% (P ≤ 0.039). HF1, HF2 and SF yielded a net reclassification improvement of 31–51% (P ≤ 0.029). Over 6.1 years, 47 cardiovascular events occurred. HF2 and SF, independent of baseline eGFR, 24-h albuminuria and other covariables were significant predictors of cardiovascular complications with risk estimates for 1-SD increases ranging from 32 to 41% (P ≤ 0.047). Conclusions The urinary proteome refines the diagnosis of existing or progressing renal dysfunction and predicts cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background Hyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population. Methods We used a nationwide database of 165 847 subjects (aged 29–74, male 40%) who participated in the annual ‘Specific Health Check and Guidance in Japan’ checkup between 2008 and 2010; we examined the relationship between serum uric acid levels at baseline and 2-year change in the estimated glomerular filtration rate (eGFR) obtained by using the Japanese equation. Results After adjusting for possible confounders, the eGFR change was inversely correlated with uric acid at baseline. In the multivariable analysis, the decline in eGFR was significantly more rapid in subjects with the slight increase in uric acid (males ≥5.7 mg/dL, females ≥4.4 mg/dL), and the risk for incidental renal insufficiency (eGFR <60 mL/min/1.73 m2) was increased at uric acid of ≥6.3 mg/dL in males and ≥5.5 mg/dL in females, compared with the lowest quintile. The multiple linear regression analysis revealed that the effect of uric acid on eGFR changes was significant, especially in females, those with proteinuria and diabetes and those without alcohol consumption. Conclusion This study showed that serum uric acid is independently associated with a more rapid decline of eGFR and incident renal insufficiency, and that a slight increase within the normal range of serum uric acid might be a risk for renal damage in the general population. [ABSTRACT FROM AUTHOR]

Background: arterial stiffening is a marker of vascular ageing and an independent risk factor for cardiovascular disease. A potential mechanism linking cardiovascular disease to chronic kidney disease might be the change in arterial elasticity. We aim to determine the association between renal function and arterial stiffness in older subjects.Design: cross-sectional study.Setting: Rotterdam study, a population-based cohort study.Subjects: we included 3,279 subjects from 1997 to 1999 with a mean age of 71.9 years.Methods: estimation of glomerular filtration rate (eGFR) was used to assess renal function. Aortic pulse wave velocity (PWV) and carotid distensibility coefficient were used as measures of arterial stiffness.Results: each standard deviation increase in eGFR, adjusting for age and sex, was associated with 0.14 m/s lower PWV [95% confidence interval (CI): −0.23, −0.05]. Further adjustments for socio-demographic and cardiovascular risk factors did not change the association (β: −0.16 m/s; 95% CI: −0.26, −0.06). There was a linear association between mean values of PWV and quartiles of glomerular filtration rate (P for trend = 0.006). There was no association between decreased renal function and carotid distensibility. There was no statistical difference in the strength of the association between renal function and PWV in subgroups of participants with and without cardiovascular risk factors.Conclusions: in this large population-based study of elderly subjects, our findings suggest that renal impairment is associated with aortic stiffness. This association is independent of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background Lupus nephritis (LN) is one of most common secondary glomerulonephritis. There is no ideal method to simultaneously assess renal structure and function in patients with LN. The aim of this study is to investigate the utility of diffusion weighted imaging (DWI) and blood oxygen level-dependent (BOLD) MR imaging in the assessment of renal involvement and pathological changes in patients with LN. Methods Sixty-five patients with LN and 16 healthy volunteers underwent coronal echo-planar DWI and BOLD MR imaging of the kidneys. The apparent diffusion coefficient (ADC) and R2* values of the kidneys were calculated with b values of 0 and 500 s/mm2. The relationship between the renal injury variables and the ADCs or R2* values were evaluated. And 16 of 65 patients with LN underwent a repeated evaluation after the induction treatment for 9 to 12 months. Results The mean ADC values of kidneys in patients with LN were 2.40 ± 0.25 × 10-3 mm2/ s, the mean R2* values of the renal cortex and medulla were 11.03 ± 1.60/sec and 14.05 ± 3.38/sec respectively, which were all significantly lower than that in volunteers. In patients with LN, the mean ADC values were correlated with eGFR (r = 0.510, p < 0.01). There was a negative correlation between the mean ADC values and renal pathology chronicity indexes (r = -0.249, p < 0.05), the R2* values of the renal medulla and proteinuria (r = -0.244, p < 0.05), and the degree of tubulointerstitial lesions (r = -0.242, p < 0.05). The ADC and R2* values of kidneys were significantly higher than those of pre-treatment in complete remission patients. Conclusions DWI and BOLD MR imaging of kidneys may be used to noninvasively monitor the disease activity and evaluate therapeutic efficacy in lupus nephritis. [ABSTRACT FROM AUTHOR]

Measurement of renal function in awake rats or mice can be accomplished by an intelligent plaster device that fits on the back of animals. The device performs a percutaneous measurement of the kinetics of a labeled fluorescent dye exclusively eliminated by the kidney. During the measurement, relative motion between plaster and skin leads to a variation of the illumination conditions, which emerge as artifacts in the data. In this paper, a novel strategy to detect and eliminate artifacts is suggested. The method combines cluster analysis and nonlinear regression with a priori knowledge about signal morphology to correct data. The performance of the proposed method is demonstrated on real and simulated data. Simulations were performed on data with two artifact amplitude ranges: (1) shifts in the recorded data with amplitude exceeding 3% of the signal amplitude for a combined duration of 10% of the total measurement time and (2) shifts greater than 3% for approximately 30% of the total measurement time. Prior to artifact removal, the MAE was calculated to be 10.3% and 21.9%, respectively. Following artifact removal using the proposed method, results showed that, when determining the half-life, the mean absolute error (MAE) was 0.88% for range type 1 and 10.4% for the more substantial range of the type 2 artifacts. When examining real data, the mean difference (bias) while determining the half-life was 7.5%. Results show that novel technique outperforms a number of state-of-the-art techniques when removing artifacts from the signal recorded while an animal is allowed to move freely. In this case, the signal acquires shifts and random changes with large amplitudes, which make it impossible to use standard methods. [ABSTRACT FROM AUTHOR]

The treatment of renal cell carcinoma (RCC) in patients diagnosed with chronic kidney disease (CKD) requires particular care in order to preserve the remaining renal function. The present study aimed to investigate the potential of a novel nephron-sparing treatment, which is capable of targeting tumors embedded deep within tissues. The present study analyzed three patients, with pre-existing CKD and multiple comorbidities, who were successfully treated for stage I RCC using the CyberKnife® stereotactic ablative radiotherapy (SABR) system. The total prescribed dose was 40 Gy in five fractions administered over five consecutive days. Treatment efficiency was determined using computed tomography scans of the tumors and periodic measurements of the glomerular filtration rate over a period of 12-40 months. Local control, defined as a radiologically stable condition, was achieved in all patients. Lung metastasis was observed in one patient nine months after SABR; however, the side-effects were generally mild and self-limiting. One patient developed renal failure 26 months after SABR, while the severity of CKD was only marginally altered in the other two patients and renal failure did not occur. In conclusion, in the present study, SABR with CyberKnife® was observed to be well tolerated in the patients, with an acceptable acute toxicity effect. Therefore, it may represent a potential therapeutic option for patients with early-stage RCC who have previously been diagnosed with CKD, but for whom other nephron-sparing treatments are contraindicated. [ABSTRACT FROM AUTHOR]

Background/Aims: In partial nephrectomy with hilar clamping every minute of ischemia can impair renal function, thus great importance is having the controlled hypotension as a part of zero ischemia technique. The aim of the study is to evaluate the effects of hypotensive anesthesia on renal function, in patients undergoing robotic assisted partial nephrectomy (RAPN) , during surgery and at 3 months follow up. Methods: This is a prospective study of 100 patients, ASA 1-2, who underwent zero ischemia RAPN under controlled hypotension (CH) from December 2011 through to May 2013. Serum creatinine, BUN, estimated glomerular filtration rates (eGFR), fractional excretion of sodium (FSE) and technetium Tc 99m mercaptoacetyltriglycine (99mTC-MAG-3), renal scintigraphy with effective renal plasma flow (ERPF) were evaluated. Results: Mean duration of CH was 50±4 minutes. Acute renal failure wasn't observed in any of the patients. A significant variation of eGFR during the procedure and 24 hours after surgery was observed. No significant variation of BUN and FSE was detected. Comparing preoperative ERPF of the operated kidney with ERPF 3 months after surgery, it decreased by 2%. Conclusion: In patients with normal preoperative renal function CH didn't show any detrimental impact on renal function during and after robotic assisted partial nephrectomy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The kidneys are a pair of vital organs that perform many functions to keep the blood clean and chemically balanced. The two most common causes of kidney disease are diabetes and high blood pressure. The National Kidney Foundation recommends three simple tests to screen for kidney disease: a blood pressure measurement, a spot check for protein or albumin in the urine, and a calculation of glomerular filtration rate based on a serum creatinine measurement. It is estimated that about 1, 00,000 persons suffer from ESRD each year of which only about 20,000 get treated. Dialysis is a process for removing waste and excess water from the blood. It is used primarily to provide an artificial replacement for lost kidney function in people with renal failure. There are benefits and complications for each type of dialysis. Attention paid by the primary health care systems to combat the rising epidemic of chronic diseases has been inadequate. This review provides the epidemiological data which helps the healthcare system to guide strategies for the prevention of kidney disease and planning for the provision of renal replacement therapy. Kidney diseases are highly prevalent globally. The risk factors for prevalence and incidence of haemodialysis are majorly hypertension and diabetes mellitus. Awareness of haemodialysis patients on the disease, medication, diet along with the life style modifications through the patient education was found to be very helpful for the patients to control their risk factors and to improve the compliance to the dosage regimen. [ABSTRACT FROM AUTHOR]