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BackgroundInterstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis.MethodsSeventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes.ResultsPatients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P ConclusionsUrinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Background Nephropathy is common in Fabry disease (FD). Prior studies of renal function during enzyme replacement therapy (ERT) have primarily used estimated glomerular filtration rate (eGFR). We studied the attrition of renal function in FD by measured GFR (mGFR) and urine protein excretion, and explored the influence of age. Methods This was a long-term observational study of a nationwide, family-screened cohort of FD patients. All Danish genetically verified FD patients on ERT, without end-stage renal disease at baseline and with three or more mGFR values were included. Results In all, 52 patients with consecutive mGFR values (n = 841) over median 7 years (range 1–13) were evaluated. Blood pressure remained normal and urine protein excretion was unchanged. Plasma globotriaosylceramide (Gb-3) levels normalized while plasma lyso-Gb-3 remained abnormal in 34% of patients. Baseline mGFR was 90 ± 3 mL/min/1.73 m2 and rate of renal function loss 0.9 ± 0.2 mL/min/1.73 m2/year. Baseline eGFR was 97 ± 5 mL/min/1.73 m2 and rate of renal function loss 0.8 ± 0.3 mL/min/1.73 m2/year. mGFR was age- adjusted to renal healthy non-FD subjects, giving a standard deviation score of −0.8 ± 0.2 with an annual slope of −0.03 ± 0.01 (P = 0.099), without differences between genders. Age grouping of age-adjusted data showed exaggerated renal function loss with age. Urine albumin–creatinine ratio (UACR) >300 mg/g was associated with faster renal function loss, independent of baseline mGFR, age and gender. Conclusions ERT-treated FD patients did not have a faster attrition of renal function than renal healthy non-FD subjects (background population). The rate of renal function loss with age was independent of gender and predicted by high UACR. We suggest cautious interpretation of non-age-adjusted FD renal data.

Background An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains uncertain. Methods We analysed 4863 non-institutionalized USA adults with CKD [defined by an estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m2 and/or a urinary albumin:creatinine ratio >30 mg/g] in a nationwide study using the National Health and Nutrition Examination Survey (NHANES) 1999–2010. Caffeine consumption was evaluated by 24-h dietary recalls at baseline and all-cause, cardiovascular and cancer mortality were evaluated until 31 December 2011. We also performed an analysis of caffeine consumption according to its source (coffee, tea and soft drinks). Quartiles of caffeine consumption were 213.5 (Q4). Results During a median follow-up of 60 months, 1283 participants died. Comparing with Q1 of caffeine consumption, the adjusted hazard ratio for all-cause mortality was 0.74 [95% confidence interval (CI) 0.60–0.91] for Q2, 0.74 (95% CI 0.62–0.89) for Q3 and 0.78 (95% CI 0.62–0.98) for Q4 (P = 0.02 for trend across quartiles). There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality. Conclusions We detected an inverse association between caffeine consumption and all-cause mortality among participants with CKD.

BACKGROUND: Numerous studies suggested that occupational or environmental exposure to lead adversely affects renal function. However, most studies lost relevance because of the substantially lower current environmental lead exposure and all relied on serum creatinine to estimate glomerular filtration. We investigated the association of estimated glomerular filtration rate (eGFR), estimated from serum creatinine, cystatin C or both, with blood lead (BPb) using the baseline measurements of the ongoing Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) in newly hired workers prior to significant occupational lead exposure. METHODS: Among 447 men (participation rate, 82.7%), we assessed the association of eGFR and the urinary albumin-to-creatinine ratio (ACR) with BPb across thirds of the BPb distribution using linear regression analysis. Fully adjusted models accounted for age, blood pressure, body mass index, the waist-to-hip ratio, smoking, the total-to-high-density-lipoprotein ratio, plasma glucose, serum γ-glutamyltransferase and antihypertensive drug treatment. RESULTS: Age averaged 28.7 (SD, 10.2) years (range, 19.1-31.8). Geometric mean BPb concentration was 4.34 μg/dL (5th-95th percentile interval, 0.9-14.8). In unadjusted and adjusted analyses, eGFR estimated from serum creatinine [mean (SD), 105.26 (15.2) mL/min/1.73 m2], serum cystatin C [mean (SD), 127.8 (13.8) mL/min/1.73 m2] or both [mean (SD), 111.9 (14.8) mL/min/1.73 m2] was not associated with BPb (P ≥ 0.36), whereas ACR [geometric mean, 4.32 mg/g (5th-95th percentile interval, 1.91-12.50)] was lower with higher BPb. CONCLUSIONS: At the BPb levels observed in this study, there was no evidence for an association between renal function and lead exposure. ispartof: NEPHROLOGY DIALYSIS TRANSPLANTATION vol:34 issue:6 pages:941-946 ispartof: location:England status: published

BackgroundFibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA).MethodsThe analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR 5%/year).ResultsAt baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P 0.05).ConclusionsOur study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

BACKGROUND: Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund–Malmö creatinine equation (LMR(Cr)) and the arithmetic mean of the LMR(Cr) and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEAN(LMR+CAPA)), as well as the Full Age Spectrum creatinine equation (FAS(Cr)) and its combination with cystatin C (FAS(Cr+Cys)), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI(Cr) and CKD-EPI(Cr+Cys)). METHODS: A total of 805 individuals, 74–93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P(30))] and the ability to detect mGFR 90%. LMR(Cr) and FAS(Cr) yielded significantly higher precision and P(30) than CKD-EPI(Cr), while bias was significantly worse. LMR(Cr), FAS(Cr) and CKD-EPI(Cr) showed similar ability to detect mGFR

Background The effect of achieved blood pressure (BP) on first stroke and renal function decline among hypertensive patients with mild to moderate chronic kidney disease (CKD) is still uncertain. Methods In total, 3230 hypertensive patients with estimated glomerular filtration rate 30-60 mL/min/1.73 m2 and/or proteinuria were included in the present analyses. Eligible participants were randomly assigned to a daily treatment of a combined enalapril 10 mg and folic acid 0.8 mg tablet or an enalapril 10 mg tablet alone. Participants were followed up every 3 months. The study outcomes included first stroke and the progression of CKD. Results The median antihypertensive treatment duration was 4.7 years. Compared with participants with a time-averaged on-treatment systolic blood pressure (SBP) of 135 to ≤140 mmHg, the incidence of total first stroke [1.7% versus 3.3%; hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in those with a time-averaged SBP of ≤135 mmHg. Furthermore, a time-averaged diastolic blood pressure (DBP) of ≤80 mmHg, compared with a time-averaged DBP level of 80 to ≤90 mmHg, was significantly related to a decreased risk of hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However, compared with participants with a time-averaged SBP of 135 to ≤140 mmHg, a lower but non-significant trend of CKD progression was found in those with a time-averaged SBP of ≤130 mmHg. Conclusions A BP treatment level of ≤135/80 mmHg, compared with a BP treatment level of 135-140/80-90 mmHg, could lead to a decreased risk of first stroke in hypertensive patients with mild-to-moderate CKD.

Author(s): Obi, Yoshitsugu; Kalantar-Zadeh, Kamyar; Streja, Elani; Daugirdas, John T | Abstract: BackgroundThe purpose of the study was to explore the precision of an equation designed to estimate residual kidney urea clearance (KRU) from interdialytic urine collection data and pre-hemodialysis (HD) serum urea nitrogen (SUN) in different hemodialysis treatment schedules.MethodsThe generalizability of the proposed equation was tested in 32 731 HD treatments where urine was collected prior to a dialysis session, mostly for 24 h but sometimes longer, in patients being dialyzed 1-4 times/week.ResultsThe residual kidney urea clearance estimating equation predicted a KRU that matched the one computed by formal modeling within 5% in g98% of sessions analyzed. The errors in estimated versus modeled KRU for interdialytic intervals (IDIs) of 2, 3, 4 and 7 days, were 1.6 ± 1.5%, -0.4 ± 1.6%, 0.9 ± 1.6%, and 1.5 ± 1.2%, respectively. Percent errors were similar for schedules of 1-4/week with the exception of urine collection during the 2-day interval of a 2:5-day twice-weekly schedule; here error averaged 5.0 ± 1.2%. Use of the average of the SUN values at the start and end of the collection period overestimated modeled KRU by 11.3 ± 4.5%, whereas an equation suggested by others underestimated modeled KRU by -9.9 ± 3.4%.ConclusionsThe equation tested predicts values for KRU that are similar to those obtained from formal urea kinetic modeling, with percent errors that only rarely exceed 5%. It gives relatively precise results for a wide range of HD treatment schedules, IDIs and urine collection periods.Keywordschronic hemodialysis, clearance, guidelines, hemodialysis, predialysis.

Background Early and accurate assessment of renal function is required for the successful detection and treatment of acute kidney injury (AKI). However, only retention parameters such as plasma urea and creatinine, and the indirect estimation of glomerular filtration rate are commonly available. Methods Here, we measured the kinetics of plasma fluorescein isothiocyanate (FITC)-sinistrin excretion to detect alterations of renal function over time in a murine model of rhabdomyolysis-induced AKI. The half-life of FITC-sinistrin was evaluated using a transcutaneous device at different time points in conscious mice, from 4 days before renal damage up to 30 days after. Retention markers were also evaluated, in parallel. Results Evaluation of the FITC-sinistrin half-life revealed early reduction of renal filtration, observed as early as 6 h after renal damage, and maintained up to 12 h following AKI. Plasma creatinine and urea levels correlated with the transcutaneous measurements of sinistrin excretion. Evaluation of sinistrin excretion also demonstrated that glycerol-treated animals did not develop AKI. Finally, histological analysis showed the presence of renal parenchymal lesions, which developed following the reduced renal filtration and persisted over time, highlighting the causative role of vascular dysfunction and myoglobin toxicity on the subsequent induction of tissue damage. Conclusions Taken together, the results of this study provide important insights into the pathophysiology of kidney injury in rhabdomyolytic mice, and indicate that the transcutaneous measurement of FITC-sinistrin is an efficient and simple method to assess renal function precisely. This method also allows reduction of the required number of experimental animals by monitoring the same mouse over time.

Background Low birthweight (LBW) is a worldwide public health problem, demonstrating an increasing incidence in developed countries, including Japan. LBW is also a risk factor for later development of chronic kidney disease (CKD). To date, studies have not evaluated the population impacts of increasing LBW rates on renal function. Methods Estimated glomerular filtration rate (eGFR) was evaluated in 3737 Japanese adolescent males (15–16 years old) using annual cross-sectional data over an 18-year period (1998–2015). Results Between the initial (1998–2003) and final (2010–15) periods of the study, the mean birthweight decreased from 3213.4 ± 383.8 to 3116.2 ± 382.3 g and the LBW rate increased from 2.5 to 5.5% (both P ≤ 0.01). Additionally, the mean eGFR decreased from 105.1 ± 15.9 to 97.4 ± 13.8 mL/min/1.73 m2 and the prevalence of mildly reduced renal function (eGFR ≤ 60–

BACKGROUND In diabetic kidney disease (DKD), it is important to find biomarkers for predicting initiation and progression of the disease. Besides glomerular damage, kidney tubular injury and inflammation are also involved in the development of DKD. The current study investigated the associations of urinary epidermal growth factor (uEGF), monocyte chemotactic protein-1 (MCP-1) and the uEGF:MCP-1 ratio with kidney involvement in patients at early and advanced stages of DKD. METHODS The concentration of uEGF and uMCP-1 was measured in two Chinese population-based studies. The associations of uEGF, uMCP-1 and uEGF/MCP-1 with occurrence of DKD were studied in a cross-sectional study (n = 1811) of early stage DKD. Associations of baseline uEGF, uMCP-1 and uEGF/MCP-1 with kidney outcome were assessed in a longitudinal cohort (n = 208) of advanced-stage DKD. RESULTS In both studies, positive correlations were found between uEGF/urine creatinine (Cr) and estimated glomerular filtration rate (eGFR) at sampling and between uMCP-1/Cr and urinary albumin:creatinine ratio (uACR). In the cross-sectional study, uEGF/Cr and uEGF/MCP-1 were negatively associated with the occurrence of DKD {odds ratio (OR) 0.65 [95% confidence interval (CI) 0.54-0.79], P

It has been demonstrated that low birth weight gives rise to a reduction in nephron number with increased risks for hypertension and renal disease. Its impact on renal function in kidney donors, however, has not been addressed.To investigate the impact of birth weight, kidney weight, kidney volume and estimated nephron number on kidney function, we collected data from 91 living kidney donors before nephrectomy, at +12, +36 and +60 months after nephrectomy.Birth weight showed a positive correlation with estimated glomerular filtration rate (eGFR) at +12, +36 and +60 months after nephrectomy (P0.05). The strongest link was observed in donors50 years old (R = 0.535, P0.001 at +12 months). Estimated nephron number and eGFR showed a strong positive correlation at +12, +36 and +60 months after nephrectomy (R = 0.540; R = 0.459; R = 0.506, P0.05). Daily proteinuria at +12 months showed a negative correlation with birth weight (P = 0.009). Donors with new-onset hypertension showed significantly lower birth weights and higher uric acid levels (P0.05). Kidney weight and volume did not show any impact on donor outcomes (P0.05).Low nephron number predisposes donors to inferior remaining eGFR, hypertension and proteinuria. The strong correlation in elderly donors may be attributed to reduced renal functional reserve due to the decline of renal function with age.

Anemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association.We followed 1094 African-Americans with hypertensive nephropathy who participated in the African-American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I(125) iothalamate) in place of eGFR.At baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was45 mL/min/1.73 m(2). For example, the absolute decline in hematocrit per 10 mL/min/1.73 m(2) decline in longitudinal eGFR was -3.7, -1.3 and -0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m(2), respectively (P0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m(2)). Similarly, male sex, younger age (65 years) and higher baseline proteinuria (protein-to-creatinine ratio0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction0.05 for each comparison). The longitudinal eGFR-hematocrit association did not differ by body mass index, serum albumin or C-reactive protein.Men, younger individuals and those with low baseline eGFR (45 mL/min/1.73 m(2)) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit.

BACKGROUND: Kidney function measured as estimated glomerular filtration rate (eGFR) is a risk factor for mortality and severe diseases. Protein intake up-regulates kidney function. The dose-response curve of eGFR over protein intake is unknown. Urinary urea nitrogen is an objective index of protein intake. METHODS: The study cross-sectionally analysed the relation between overnight urinary urea nitrogen ((on)U-ureaN) and eGFR with and without control for other variables in 4106 adults of the Gubbio population. Analyses were done for serum creatinine (S-cr) also to investigate the independency of results from eGFR calculation. RESULTS: Higher (on)U-ureaN associated with higher eGFR, and lower S-cr independently of sex and age (simple and partial correlation coefficients >0.100, P < 0.001). Analyses by (on)U-ureaN decile indicated sigmoid curves of eGFR and S-cr over (on)U-ureaN with trend to flatness in the lowest 20% and the highest 20% of (on)U-ureaN (10.12 mg/h, respectively). Multi-variable spline regression indicated that the relation of eGFR over (on)U-ureaN was non-significant for (on)U-ureaN 10.12 mg/h (coefficient = +0.05, 95% CI = -0.06/ +0.16, P = 0.394). eGFR differed by ≈8 mL/min × 1.73 m(2) between the lowest and highest 20% of (on)U-ureaN distribution. CONCLUSIONS: Higher protein intake relates to higher eGFR. The relation is sigmoid with eGFR up-regulation for (on)U-ureaN >5.19 mg/h, a threshold approximately corresponding to the recommended daily allowance for protein intake (0.8 g/day per kg of ideal weight).

Background Emerging research has identified the endothelin (ET)-1 pathway as a potential target for novel renoprotective therapies. We recently showed that selective ET-A receptor antagonism in chronic renovascular disease (RVD) improves renal function and reduces renal injury. Although ET-A and -B have opposing roles, in some clinical situations they may induce similar effects. Thus, we hypothesized that simultaneous blockade of the ET-A and -B receptors would protect the kidney during RVD. Methods Unilateral RVD was induced in pigs. After 6 weeks, single-kidney function was quantified in vivo using multi-detector computer tomography. Pigs were subsequently divided into untreated (RVD, n = 7) or daily-treated with the dual ET-A/B receptor antagonist macitentan (RVD + macitentan, n = 6) for 4 weeks. At 10 weeks, in vivo studies were repeated, then pigs were euthanized and ex vivo studies performed in the stenotic kidney to quantify inflammation, fibrosis, microvascular density and remodeling. Results Four weeks of macitentan therapy modestly improved renal blood flow (29%, P = 0.06 versus pre-treatment) and showed protective effects on the renal parenchyma by attenuating inflammation and glomerulosclerosis, reducing apoptosis and tubular casts and improving albuminuria and cortical microvessel density. No overt adverse effects were observed. Conclusion Possibly by inducing a pro-survival renal microenvironment, macitentan increased renal microvascular density, promoted cell survival and decreased injury, which in turn improved stenotic kidney hemodynamics in our model. Our results further support the safety of using macitentan in patients with concomitant chronic renal disease and supported the feasibility of a new strategy that may preserve the stenotic kidney in RVD.

Background: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. Methods: Data from 5085 CKD patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) of 30–

Background. Recent studies have shown an increasing risk of hypothyroidism with incrementally lower estimated glomerular filtration rate (eGFR) in cohorts comprised of patients with normal to mildly impaired kidney function. We sought to confirm these findings in a nationally representative cohort of Veterans Affairs patients with moderate-to-severe chronic kidney disease (CKD). Methods. This study examined the association between kidney function and hypothyroidism among 461 607 veterans with Stage 3 to 5 CKD who underwent repeated measurements of serum creatinine and thyrotropin (TSH) at identical time points between October 2004 and September 2006. Kidney function was defined by eGFR using the Chronic Kidney Disease Epidemiology Collaboration formula. In primary analyses, the association between eGFR and hypothyroidism (defined as serum TSH > 5 mIU/L and/or receipt of thyroid hormone supplementation) was estimated using multivariable random effects logistic regression. In secondary analyses, the association between eGFR and serum TSH level was estimated using multivariable random effects linear regression. Results. At baseline, 68.9, 25.5, 5.3 and 0.3% of patients had Stage 3A, 3B, 4 and 5 CKD, respectively. For every 10 mL/ min/1.73 m 2 lower eGFR, there was an 18% higher risk of hypothyroidism: adjusted odds ratio 1.18 [95% confidence interval (CI) 1.17–1.20, P < 0.001]. In secondary analyses, we observed that a 10 mL/min/1.73 m 2 lower eGFR was associated with a 0.11 mIU/L higher serum TSH (95% CI 0.10– 0.11 mIU/L higher serum TSH, P < 0.001). Conclusions. In a nationally representative cohort of patients with moderate-to-severe CKD, there is an inverse association between eGFR and risk of hypothyroidism.

The progression of diabetic nephropathy (DN) is frequently determined by clinical parameters; however, the predictive value of histologic lesions remains largely unknown. Our aim was to evaluate the relationship between histologic changes and renal outcome in patients with type 2 diabetes mellitus (T2DM).A total of 396 patients with T2DM and biopsy-proven DN who received follow-up for at least 1 year were recruited. The severity of different histologic lesions was assessed using the pathologic classification established by the Renal Pathology Society. Renal outcomes were defined by progression to end-stage renal disease and doubling of serum creatinine. The influence of histologic findings on renal outcomes was assessed using univariate and multivariate Cox regression.A univariate Cox regression showed that the severity of glomerular and interstitial lesions had a significant impact on renal outcomes (P0.001). Scores of vascular lesions demonstrated no association with renal outcomes (P0.05). A multivariate COX analysis demonstrated that the glomerular classes and scores of interstitial fibrosis and tubular atrophy were significantly associated with renal outcomes when adjusting for baseline proteinuria, mean arterial pressure and estimated glomerular filtration rate (P0.05). The glomerular and interstitial lesions correlated significantly among each other. However, in several patients, the severity of interstitial lesions did not correlate with glomerular lesions.These findings indicated that the severity of glomerular and interstitial lesions were significantly associated with renal outcomes in patients with DN, whereas the vascular indexes did not have any impact on renal outcomes.

BACKGROUND Drinking eight glasses of fluid or water each day is widely believed to improve health, but evidence is sparse and conflicting. We aimed to investigate the association between fluid consumption and long-term mortality and kidney function. METHODS We conducted a longitudinal analysis within a prospective, population-based cohort study of 3858 men and women aged 49 years or older residing in Australia. Daily fluid intake from food and beverages not including water was measured using a food frequency questionnaire. We did multivariable adjusted Cox proportional hazard models for all-cause and cardiovascular mortality and a boot-strapping procedure for estimated glomerular filtration rate (eGFR). RESULTS Upper and lower quartiles of daily fluid intake corresponded to >3 L and

Background. Men commence dialysis with a higher estimated glomerular filtration rate (eGFR) than women and are more likely to transition from chronic kidney disease (CKD) to endstage renal disease. We hypothesized that for a given estimated body surface area (BSA) men have a greater metabolic burden, and that consequently, the practice of indexing GFR to BSA results in gender differences in the degree of biochemical uraemia. Methods. Metabolic burden was assessed as estimated dietary protein, calorie, phosphorus, sodium and potassium intakes and urinary urea nitrogen excretion in the Chronic Renal Insufficiency Cohort, Modification of Diet in Renal Disease study, and National Health and Nutrition Examinations Surveys (NHANES) 1999–2010. Uraemia was characterized by serum biochemistry. Results. Per m 2 BSA, men had greater urea nitrogen excretion and intakes of all dietary parameters (P < 0.001 for all). For a given BSA-indexed iothalamate GFR or eGFR, male gender was associated with a 10–15% greater serum urea nitrogen (P < 0.001), giving men with a BSA-indexed GFR of 70–75 mL/min/1.73 m 2 the same serum urea nitrogen concentration as women with a GFR of 60 mL/min/1.73 m 2 . However, indexing metabolic burden and GFR to alternative body size measures (estimated total body water, lean body mass or resting energy expenditure) abolished/reversed the gender associations. In NHANES, BSA-indexed eGFR distribution was very similar for men and women, so that adjusting for eGFR had little effect on the gender difference in serum urea. Conclusions. Indexing GFR to BSA across genders may approximate nature’s indexing approach, but gives men a greater ingested burden of protein, calories, sodium, phosphorus and potassium per mL/min GFR. This has implications for gender differences in CKD outcomes.

BACKGROUND Kidney transplants from living donors with an estimated glomerular filtration rate (eGFR) < 80 mL/min per 1.73 m(2) may be at risk for increased graft loss compared with a recipient who receives a kidney from a living donor with a higher eGFR. METHODS This retrospective cohort study considered 2057 living kidney donors and their recipients from July 1993 to March 2010 at five centres in Ontario, Canada, and linked them to population-based, universal healthcare databases. Recipients were divided into five groups based on their donor's baseline eGFR. The median (inter-quartile range) for the lowest eGFR group was 73 (68-77) mL/min per 1.73 m(2). Subjects were followed for a median of 6 years (IQR: 3-10 years). RESULTS There was no significant difference in the adjusted hazard ratio (HR) for graft loss when comparing recipients in each eGFR category to the referent group (≥110 mL/min per 1.73 m(2)). The adjusted HRs (95% CI) from the lowest (

BackgroundIschaemia-reperfusion injury (IRI) to the kidney is a complex pathophysiological process that leads to acute renal failure and chronic dysfunction in renal allografts. It was previously demonstrated that during IRI, hyaluronan (HA) accumulates in the cortical and external medullary interstitium along with an increased expression of its main receptor, CD44, on inflammatory and tubular cells. The HA-CD44 pair may be involved in persistent post-ischaemic inflammation. Thus, we sought to determine the role of HA in the pathophysiology of ischaemia-reperfusion (IR) by preventing its accumulation in post-ischaemic kidney.MethodsC57BL/6 mice received a diet containing 4-methylumbelliferone (4-MU), a potent HA synthesis inhibitor. At the end of the treatment, unilateral renal IR was induced and mice were euthanized 48 h or 30 days post-IR.Results4-MU treatment for 14 weeks reduced the plasma HA level and intra-renal HA content at 48 h post-IR, as well as CD44 expression, creatininemia and histopathological lesions. Moreover, inflammation was significantly attenuated and proliferation was reduced in animals treated with 4-MU. In addition, 4-MU-treated mice had a significantly reduced expression of α-SMA and collagen types I and III, i.e. less renal fibrosis, 30 days after IR compared with untreated mice.ConclusionOur results demonstrate that HA plays a significant role in the pathogenesis of IRI, perhaps in part through reduced expression of CD44. The suppression of HA accumulation during IR may protect renal function against ischaemic insults. © 2013 The Author. All rights reserved.

Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown.The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: 'none' (no exposure prior to surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or 'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were 'functional' AKI based upon changes in pre- to postoperative serum creatinine, and 'structural AKI', based upon peak postoperative levels of four urinary biomarkers of kidney injury.Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.

BACKGROUND: In Mexican Americans, the IRS1 G972R polymorphism (rs1801278) has been associated to such a marked reduction in glomerular filtration rate (GFR) (i.e. β = −8.3 mL/min/1.73 m(2)) to be considered a major determinant of kidney function. METHODS: This was a cross-sectional study to investigate whether a similarly strong effect can also be observed among individuals of European ancestry. We investigated a total of 3973 White patients with type 2 diabetes. Standardized serum creatinine was measured by the modified kinetic Jaffè reaction and estimated GFR (eGFR) calculated by the modification diet renal disease (MDRD) formula; rs1801278 was genotyped by TaqMan assay. RESULTS: No significant association was observed, with R972 carriers showing only a modestly, not significant, lower eGFR level as compared with other subjects (β = −1.82 mL/min/1.73 m(2), P = 0.086). CONCLUSIONS: Our data indicate that IRS1 G972R is not a strong determinant of GFR in diabetic patients of European ancestry as in Mexican Americans. Since we had 100% power to detect the previously reported association, the risk our finding is a false negative one is minimal.

Glomerular filtration rate estimates (e-GFR) are often used to evaluate the changes in renal function, but have not been validated for this purpose in kidney transplant recipients (KTRs). The aim of this study was to evaluate the validity of e-GFR for monitoring serial changes in renal function in KTR using directly measured GFR by inulin clearance (I-GFR) as the reference standard.Performances of inverse serum creatinine (1/creat) and Cockcroft and Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulas were assessed to estimate the changes in I-GFR.A total of 1935 I-GFR clearance procedures were performed in 631 KTRs who underwent serial measurements between 2003 and 2009. The baseline median I-GFR were 51.0 mL/min/1.73 m(2) (confidence interval 95%: 23-84 mL/min/1.73 m(2)]. The performances of 1/creat and formulas for detecting the I-GFR variations between two consecutive measurements (n = 1304) were similar. To detect the variations of20% (increase or decrease), sensitivities ranged between 50 and 56%, and specificities between 64 and 69%. To detect the variations20% (increase or decrease), sensitivities ranged between 27% and 39%, and specificities between 88 and 97%. Bland-Altman plots confirmed the scattering of values for individual patients.In a population of Caucasian KTRs, the mean changes in GFR are correctly estimated whatever the formula used in the range of 23-84 mL/min/1.73 m(2) and can thus be applied in population studies. However, in clinical practice, individual changes in GFR evaluated by formulas should be interpreted with caution in KTRs.

There is a lack of high-quality evidence that advocates the use of corticosteroids for IgA nephropathy (IgAN) with minimal change-like lesions (also called IgAN with minimal change disease, MCD-IgAN).Twenty-seven biopsy-proven adult MCD-IgAN patients were enrolled. Daily single dose of 1 mg/kg (maximum 60 mg/day) prednisone was given until complete remission (CR), followed by gradually decreasing dosage. The clinical data were collected from baseline up to 12 weeks of treatment (Certification No. 2011NLY-006, Clinical trials gov ID. NCT01451710).The patient cohort consisted of 15 males and 12 females. The mean age of the patients was 29.2 ± 10.8 years (range 18-60 years) at the time when they were subject to renal biopsy. All patients had hypoalbuminaemia (23.7 ± 4.13 g/L) and heavy proteinuria (3.5 g/24 h). Cumulative CR (proteinuria0.4 g/24 h) rates were 3.70, 48.1, 92.6 and 100% after 1, 2, 4 and 8 weeks of treatment, respectively. Two cases relapsed after CR, one at 6 weeks of treatment, likely due to failure to follow the corticosteroid withdrawal schedule, and the other one at 8 weeks of treatment accompanied with an upper respiratory infection. Infection, alanine aminotransferase elevation (2-folds), fasting blood glucose (FBG) elevation (6.2 mmol/L) and hypopotassaemia (3.5 mmol/L) occurred in 2, 5, 2 and 5 cases, respectively, but were eliminated after treatment.Corticosteroid therapy is likely effective and safe for MCD-IgAN patients.

Background. Some adult patients with minimal change nephrotic syndrome (MCNS) who are refractory to steroid treatment or combination with immunosuppressive drug developed reversible acute renal failure (ARF) due to persistent severe hypoalbuminemia and proteinuria. It is a challenge to find rescue therapies that are effective and safe in treating such difficult patients. Methods. In this prospective observational study, 13 patients with adult-onset MCNS, all unresponsive to treatment with a steroid or a steroid with other immunosuppressive drugs, were studied from January 2005 to February 2009. All patients developed ARF before enrollment. Oral tacrolimus (TAC) was started at 1 mg/day (target trough levels of 3–6 ng/mL) before serum creatinine (SCr) decreased to ≤133 μmol/L, and then increased doses were given (target trough level of 5–10 ng/mL) when SCr decreased to ≤133 μmol/L. Primary outcome variables were remission, and recovery from ARF. Secondary outcome variables were time to recovery from ARF, time to remission, relapse rate, changes in SCr and estimated glomerular filtration rate (eGFR). Results. One patient discontinued TAC due to deterioration of ARF, and 12 patients recovered from ARF. The mean time to recovery from ARF was 15.8 ± 4.4 days. Nine patients (69.2%) experienced complete remission (CR) and two patients (15.4%) experienced partial remission (PR). The mean time to PR and CR was 4.8 ± 2.7 and 9.4 ± 2.3 weeks, respectively. After a mean follow-up of 69.6 months, 36.4% (4/11) of patients who had remission experienced relapses. One patient who was resistant to TAC therapy had a doubling of serum creatinine concentration during follow-up. Conclusions. TAC may be a suitable therapeutic option for treatment of adult-onset refractory MCNS with reversible ARF.

Background. To determine the incidence and significance of acute kidney injury (AKI) after initiating highly active antiretroviral therapy (HAART). Methods. A prospective cohort study of 271 consecutively treated HIV-infected patients, initiating first (75) or sequential HAART (196) from January 2008 to June 2011. AKI was diagnosed according to the Risk, Injury, Failure, Loss of kidney function, End-stage renal disease (RIFLE)/Acute Kidney Injury Network (AKIN) criteria, and the risk of progression to chronic kidney disease (CKD) was evaluated. Results. A greater estimated glomerular filtration rate (eGFR) decrease after 1 year was observed for patients initiating a tenofovir disoproxil fumarate (TDF)-based regimen (�6.45 versus +0.98 mL/min/1.73 m 2 when compared with patients without TDF; P < 0.01), both in the case of the first (�8.5 versus �2.27; P = 0.04) or successive regimens (�5.3 versus + 1.18 mL/min/1.73 m 2 ; P < 0.01). AKI, as defined, was observed in 10% (28 cases, 6.98 episodes/100 patients-year), mostly stage I (27 cases), in a median time of 6 (3–16.5) months. Four cases (14%), having a worse baseline renal function progressed to CKD, whereas four recovered completely. In the multivariate analysis, AKI was associated with the concomitant use of cotrimoxazole prophylaxis and to low CD4+ count. CKD was diagnosed in 2% (six cases) of patients. Therefore, the overall rate of HAART-associated renal disorders was 11% (30 cases, 7.46 episodes/100 patients-year (95% confidence interval, 6.09–8.83). Conclusions. The initiation of a tenofovir-based regimen is followed by a significant decline in eGFR, although it could be misinterpreted by the concomitant use of cotrimoxazole. A substantial proportion of patients develop AKI, but only a minority progress to CKD. Patients initiating HAART and developing AKI should be carefully monitored for progression of renal disease.

BACKGROUND: Serum metabolites are associated cross-sectionally with kidney function in population-based studies. METHODS: Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic kidney disease (CKD) incidence over 7 years in 1104 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 study. RESULTS: Corrected for multiple testing, a significant association with annual change in the estimated glomerular filtration rate was observed for spermidine (P = 5.8 × 10-7) and two metabolite ratios, the phosphatidylcholine diacyl C42:5-to-phosphatidylcholine acyl-alkyl C36:0 ratio (P = 1.5 × 10-6) and the kynurenine-to-tryptophan ratio (P = 1.9 × 10-6). The kynurenine-to-tryptophan ratio was also associated with significantly higher incidence of CKD at the follow-up visit with an odds ratio of 1.36 per standard deviation increase; 95% confidence interval 1.11-1.66, P = 2.7 × 10-3). In separate analyses, the predictive ability of the metabolites was assessed: both the three significantly associated metabolite (ratios) as well as a panel of 35 metabolites selected from all metabolites in an unbiased fashion provided as much but not significantly more prognostic information than selected clinical predictors as judged by the area under the curve. CONCLUSIONS: Baseline serum concentrations of spermidine and two metabolite ratios were associated with kidney function change over subsequent years in the general population. In separate analyses, baseline serum metabolites were able to predict incident CKD to a similar but not better extent than selected clinical parameters. Our longitudinal findings provide a basis for targeted studies of certain metabolic pathways, e.g. tryptophan metabolism, and their relation to kidney function decline. KEYWORDS: GFR, incident chronic kidney disease, kidney function loss, metabolites, prediction &nbsp

BACKGROUND Chronic kidney disease (CKD) is associated with a poor quality of life and cardiovascular events and is a great threat to public health. METHODS We investigated the trends of CKD prevalence over 12 years in Korean adults at least 20 years old using sampling weight methods based on the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998), II (2001), III (2005) and IV (2007-09). Of the 135 954 subjects participating in KNHANES I-IV, 33 276 (14 307 men, 18 969 women) were included in the present study. RESULTS The percentage of glomerular filtration rate (GFR)

Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function.We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning).Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b=0.21SD decline per unit ln(eGFR), 95% CI: 0.04-0.38, P=.018], verbal episodic memory [b=0.28 SD decline per unit ln(eGFR), 95% CI: 0.02-0.54, P=0.038] and abstract reasoning [b=0.36 SD decline per unit ln(eGFR), 95% CI: 0.04-0.67, P=0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke.Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline.

Background. The aim of this study was to evaluate the role of hypomagnesemia as a risk factor for the development of acute kidney injury (AKI) and non-recovery of renal function in critically ill patients. Methods. A cohort study was conducted by collecting data from March to June 2011 in 232 patients who were admitted into an intensive care unit (ICU). Magnesium serum levels were measured daily during ICU stay. Hypomagnesemia was defined as an episode of serum magnesium concentration of

Background. Preemptive transplantation is associated with better survival and transplant outcomes than transplantation after dialysis has been started. The purpose of this study is to examine associations between candidate characteristics, likelihood of preemptive transplant, candidate survival and renal function (RF) at the time of listing. Methods. We looked at 57 677 solitary renal transplant candidates from the Scientific Registry of Transplant Recipients database listed prior to dialysis from 2000 to 2009. Using multivariable models, we measured associations between candidate characteristics, likelihood of preemptive transplantation, candidate survival and RF at listing. Results. Candidates with higher RF at listing were more likely to be male, Caucasian, diabetic, be a prior transplant recipient and have more education. Higher RF at listing was strongly associated with greater likelihood of receipt of preemptive transplant [adjusted odds ratio ¼ 1.45, 95% confidence interval (CI) 1.38–1.51] and conferred a significant survival advantage [adjusted hazards ratio ¼ 0.84, 95% CI 0.79–0.89, per 5 mL/min/1.73 m 2 ]. Conclusions. Patient characteristics associated with higher RF at listing suggest differences in access to care. Given that higher RF at the time of listing was also significantly associated with greater likelihood of preemptive transplantation and better survival prior to transplantation, our results suggest that listing at higher levels of RF may improve transplant candidate outcomes.

Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects.This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV.ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (30 years) had higher GFR than young men but the reverse was recorded in the elderly (65 years). There was no difference in GFR between obese (BMI30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable.There are several significant differences in GFR and ECV between healthy men and women.

Introduction. Pregnancy during dialysis is a high-risk condition which is becoming more and more common. The renal outcome of children born from such pregnancies needs to be investigated since renal development may be affected (i.e. exposure to uraemic toxins, therapies, intermittent haemodynamic changes during sessions, prematurity, growth retardation). Methods. We performed a single-centre prospective global and renal evaluation (inulin clearance or 2009 Schwartz formula in children

In the kidney, immunoglobulin light chain amyloidosis (AL) can be deposited in vascular-limited AL (V-AL) or diffuse (D-AL) pattern. These patterns are associated with different clinical presentations. A nested case study was performed to describe these differences. V-AL was defined by the vascular-limited deposits. Cases were matched for age, sex and date of renal biopsy. There were 12 cases of V-AL (mean age 61 ± 11 years) and 24 cases of D-AL. Median follow-up was 26 months for V-AL and 38 months for D-AL, P = 0.14. Lambda was more common in D-AL (83.3%) than V-AL (50%, P = 0.04). Cardiac function was similar between the two groups. V-AL patients presented with lower renal function (serum creatinine = 2.1 versus 1.3 mg/dL, P = 0.02; estimated glomerular filtration rate 31 versus 59 mL/min/1.73m(2), P = 0.01 and creatinine clearance 38.5 versus 64 mL/min/1.73m(2), P = 0.02, respectively). Proteinuria was low grade in V-AL [0.4 (0.09-0.98) g/day] compared to nephrotic range in D-AL patients [8.0 (0.2-22) g/day, P < 0.001]. Stem cell transplantation was performed on 62.5% of the D-AL but on only 25% of the V-AL, P = 0.08. Median survival was longer in patients with D-AL (77.2 months) versus V-AL (40.6 months, log-rank P = 0.02). Our study found that V-AL patients presented with more severe renal insufficiency and less proteinuria than D-AL. There was a preference for λ light chain in the D-AL that was not noted in the V-AL. Patients with D-AL in this study had a longer median survival but most of them were stem cell transplantation candidates.

Background. Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with non-diabetic nephropathy in African Americans. ApoL1 proteins associate with high-density lipoprotein (HDL) particles in the circulation. Plasma HDL particle subclass concentrations were compared in 73 African Americans based on APOL1 genotypes to detect differences potentially contributing to renal disease. Methods. HDL subclass concentrations were measured using nuclear magnetic resonance spectroscopy in African American first-degree relatives of patients with non-diabetic end-stage renal disease. Participants had estimated glomerular filtration rates (GFRs) > 80 mL/min and lacked albuminuria. Additive effects of the number of APOL1 risk variants on natural logarithm-transformed HDL subclass concentrations were computed. Results. Participants were 58.9% female with mean ± SD age 47.2 ± 13.3 years and GFR 92.4 ± 18.8 mL/min. The numbers with 2, 1 and 0 APOL1 nephropathy risk variants, respectively, were 36, 17 and 20. Mean ± SD medium-sized HDL concentrations were significantly lower for each additional APOL1 risk variant (2 versus 1 versus 0 risk variants: 9.0 ± 5.6 versus 10.1 ± 5.5 versus 13.1 ± 8.2 μmol/L, respectively; P = 0.0222 unadjusted; P = 0.0162 triglyceride- and ancestry adjusted). Conclusions. Lower medium-sized HDL subclass concentrations are present in African Americans based on increasing numbers of APOL1 nephropathy risk variants. Potential mechanistic roles of altered medium HDL concentrations on APOL1-associated renal microvascular diseases should be evaluated.

Background. FTY720 (fingolimod), a novel immunomodulator, has demonstrated potential for prevention of acute rejection in combination with cyclosporine.Methods. This study evaluated FTY720 2.5 mg versus mycophenolate mofetil (MMF) in a combination regimen with standard tacrolimus and corticosteroids in de novo renal transplant recipients for the composite efficacy within 6 months of transplantation.Results. Incidence of treated biopsy-proven acute rejection was 22.9% with FTY720 and 18.5% with MMF. Increased incidence of macular oedema, transient decrease in heart rate and low rate of infections were seen in the FTY720 arm.Conclusion. FTY720 combined with tacrolimus and steroids did not show a significant therapeutic advantage over MMF for the prevention of acute rejection in de novo renal transplant recipients. © The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Introduction/objectives. Though recent research has concluded that revascularization of atherosclerotic renal artery stenosis has no benefit for most patients, negative findings of the Angioplasty and STent for Renal Artery Lesions (ASTRAL) trial have been criticized in professional fora. Aim of the current study was to determine whether patients undergoing renal revascularization outside of ASTRAL showed any benefit. If so, could we determine a patient group that would benefit from intervention? Methods. Patients undergoing renal revascularization outside of the ASTRAL trial between 2003 and 2007 at our institution were reviewed. The primary comparison was the rate of decline of renal function based on individual reciprocal creatinine plots for the periods leading up to and following revascularization. Those who showed any improvement in the mean slope were compared to those with a negative or neutral response. Results. One hundred and twenty-seven patients underwent renal revascularization outside of ASTRAL. The majority [79 (62%)] showed some improvement in the rate of change in renal function, though overall this failed to reach statistical significance. Those who responded positively tended to be declining faster prior to intervention; they were less likely to require RRT (6 versus 29%), and if they did, it was significantly later (3.6 versus 0.7 years). Mortality was, however, similar in both groups. Subgroup analysis was undertaken of patients in whom kidney function was rapidly deteriorating prior to revascularization. The rate of change in this group showed a more sizeable improvement (P = 0.05). Nonetheless, a similar proportion of both groups required RRT and there was no evidence of improvement in overall mortality. Conclusions. In keeping with ASTRAL’s findings, our use of renal revascularization has produced no demonstrable benefit overall. There was a suggestion of benefit in patients with rapidly declining renal function in terms of delaying the need for renal replacement therapy, but improvements in cardiovascular outcomes have yet to be proven.

Background. Metabolic syndrome has been recently identified as a risk factor for chronic kidney disease (CKD). Since the five individual components of the metabolic syndrome have also been identified as risk factors for CKD, the metabolic syndrome diagnosis may represent an aggregate of CKD risk factors. On the other hand, the components of the metabolic syndrome are also associated with insulin resistance, which may directly mediate the increased CKD risk. Methods. This study was a cross-sectional evaluation of the relationship between metabolic syndrome, insulin resistance and estimated glomerular filtration rate (eGFR) in 574 non-diabetic individuals. Insulin resistance was directly quantified using the insulin suppression test, and the metabolic syndrome components were measured. eGFR was calculated using the three validated estimation equations: the Chronic Kidney Disease Epidemiology Collaboration equation, the Mayo quadratic equation and the Modification of Diet in Renal Disease study equation. Results. While CKD prevalence was higher and mean eGFR was lower in individuals who met the metabolic syndrome criteria compared with those who did not, we did not observe a significant relationship between insulin resistance and eGFR. Of all of the components of the metabolic syndrome, only hypertension was significantly associated with CKD prevalence [odds ratio (95% confidence interval), 3.5 (1.2–10.1), P ¼ 0.02]. Conclusion. Although CKD is more common among individuals with the metabolic syndrome, insulin resistance is not a common factor.

Background. In dialysis patients, cross-sectional studies show that total and abdominal body fat associate with inflammatory markers. Whether this is true in earlier disease stages is unknown. We evaluated the cross-sectional and longitudinal (12-month interval) association between body fat markers and C-reactive protein (CRP) in pre-dialysis chronic kidney disease (CKD) patients. Methods. We studied, over a period of 1 year, clinically stable CKD patients at Stages 3–4 who were under treatment in a single outpatient clinic. Fifty-seven patients were included and 44 concluded the observational period [males: 66%; age: 62.96 13.9 years; body mass index (BMI): 25.5 6 5.1 kg/m 2 ; estimated glomerular filtration rate (eGFR): 34 6 12.3 mL/min/1.73m 2 ]. Total body fat (skinfold thicknesses), waist circumference (WC), laboratory measurements (serum creatinine, total cholesterol, albumin, high-sensitivity CRP and leptin) and food intake (24-h food recall) were assessed at baseline and after 12 6 2m onths. Results. Most patients had anthropometric parameters in the range of overweight/obesity and none had signs of protein-energy wasting. In univariate analysis, changes (delta: end—baseline) in CRP were associated (P < 0.05) with changes in BMI (r ¼ 0.39) and WC (r ¼ 0.33). In multiple regression analysis, these associations remained significant (P < 0.05) even after adjusted by potential confounders (sex, diabetes, baseline age and eGFR). Conclusions. During a follow-up of 12 months, changes in BMI and WC were directly associated with changes in CRP. Our results support the concept that interventions aimed at reducing weight and/or abdominal adiposity in pre-dialysis CKD patients may also translate into reduced systemic inflammation.

Background. Renal AA amyloidosis presents as a lifethreatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. Methods. A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and antihypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein–creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. Results. Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr

BACKGROUND The adverse histological features predicting a progressive loss of renal function in idiopathic membranous nephropathy (IMN), before the establishment of impaired renal function with advanced glomerulosclerosis and/or interstitial fibrosis, are still poorly understood. The present study examined the relationship between the glomerular density (GD; non-sclerotic glomerular number/renal cortical area of biopsy) and the renal prognosis in IMN patients, especially in those without any apparent renal dysfunction at the time of diagnosis. METHODS The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed in the 65 IMN patients with an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m(2) (mean, 80 mL/min/1.73 m(2)) at biopsy. RESULTS The individual values for GD ranged from 1.6 to 6.5/mm(2) with 4-fold variation. A lower GD was associated with progression based on a ≥ 50% reduction in eGFR or reaching to end-stage renal disease. An association between a lower GD and progression was observed, especially in patients with persistent proteinuria of ≥ 1 g/day at follow-up. In contrast, any patients who achieved proteinuria of