Design, setting, participants, & measurements: A one-compartment pharmacokinetic model of creatinine change resulting from a decrease in GFR was applied to a population of 10,000 simulated virtual inpatients. Treatment was simulated as an amelioration of GFR decrease by a specified percentage, the treatment efficacy, in 50%. Three categorical and two continuous outcome metrics were calculated and compared. Outcomes were compared for measured and estimated baseline creatinine levels that were back-calculated assuming a GFR of 100 or 75 ml/min.

Results: The continuous metrics, the average value of creatinine and the average value of creatinine relative to baseline decreased approximately linearly with increase in treatment efficacy. The categorical metrics displayed a sigmoidal decrease and erroneously suggested perfect treatment when GFR decrease was ameliorated by only 60 to 80%. Using an estimate of baseline creatinine increased the number of patients who were classified as having AKI.

Conclusions: When used to determine clinical trial outcome, continuous metrics correctly detected the extent of intervention. At low treatment efficacy, categorical metrics underestimated and at high treatment efficacy overestimated the effect of treatment. These effects were exaggerated when the population contained a high proportion of patients with more severe AKI. An estimated baseline creatinine level will overestimate AKI prevalence compared with a measured baseline value. Clinical trials of AKI should use a continuous outcome metric and a measured baseline and report baseline median and interquartile range.

Design, setting, participants, & measurements: We studied 295 patients with different stages of nondiabetic CKD (52% male; age 47 ± 12 yr), testing the association between sTWEAK plasma levels and CKD stage and the relationship between flow-mediated dilation (FMD) and sTWEAK concentrations. Fifty-five healthy volunteers (51% male; age 47 ± 11 yr) served as matched control subjects.

Results: A gradual decrease in FMD was observed as eGFR decreased. Compared with healthy control subjects, sTWEAK plasma levels were diminished in all stages of CKD and correlated strongly with eGFR. FMD levels were associated with sTWEAK concentrations in univariate analysis. This association persisted after multivariate adjustment for eGFR levels, high-sensitivity C-reactive protein, diastolic BP, and sTWEAK, all of which were found to be significant and independent contributors to FMD.

Conclusions: A decline in eGFR is accompanied by gradual reductions in sTWEAK plasma levels. Because sTWEAK strongly and independently correlated with FMD, our study suggests novel links between sTWEAK and endothelial dysfunction in patients with CKD.

Design, setting, participants, & measurements: In the Chronic Kidney Disease in Children Cohort (aged 1 to 16 yr), we measured GFR by plasma disappearance of iohexol (iGFR) and biomarkers in the first two annual visits. Models took the form GFR₂ = a[GFR₁/40]^b[X₂/X₁]^c, where GFR₂ and GFR₁ represented the current and previous years' iGFR, 40 ml/min per 1.73 m² was the cohort mean, and X₂/X₁ was the change in predictors over time. Using data from 360 participants with a median age of 12.1 yr, we evaluated the predictive performance of a past GFR measurement and 20 other variables using a two-thirds random sample of the data. A one-third sample was reserved for validation.

Results: Previous iGFR measurements were strongly predictive of subsequent iGFR and adding change in height/serum creatinine significantly improved the explanatory power to 78%. In the validation set, the correlation between estimated and measured GFR was 0.88, and 48 and 88% of estimated GFRs were within 10 and 30% of observed iGFRs. When the past GFR measurement was not used, addition of change in markers to a cross-sectional model did not improve prediction.

Conclusions: Longitudinal formulas to estimate iGFR capitalize on the high predictive power of previous iGFR measurements and in this study yielded a parsimonious prediction model with the potential for assessing progression in the clinical setting.

Design, setting, participants, & measurements: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.

Results: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.

Conclusions: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

Design, setting, participants, & measurements: Thirty-nine GSD I patients that visited our clinic were studied. GFR and effective renal plasma flow (ERPF) were measured by means of I¹²⁵ iothalamate and I¹³¹ hippuran clearance and corrected for body surface area. Microalbuminuria was defined as >2.5 mg albumin/mmol creatinine and proteinuria as >0.2 g protein per liter. Optimal metabolic control was present when blood glucoses were >3.5 mmol/L, urine lactate/creatinine ratios <0.06 mmol/mmol, triglycerides <6.0 mmol/L, and uric acid concentrations <450 µmol/L.

Results: Quadratic regression analysis showed a biphasic pattern in the course of GFR and ERPF related to age. Microalbuminuria was observed significantly less frequently in the patients with optimal metabolic control compared with the patients with nonoptimal metabolic control. A significant decrease in GFR was observed after starting ACE inhibition.

Conclusions: This study describes a biphasic pattern of the natural course of GFR and ERPF in GSD I patients, followed by the development of microalbuminuria and proteinuria. Optimal metabolic control has a renoprotective effect on the development of microalbuminuria and proteinuria in GSD I patients. Treatment with ACE inhibitors significantly decreases the GFR, especially in GSD I patients with glomerular hyperfiltration.

Design, setting, participants, & measurements: We studied renal biopsies with FSGS, not otherwise specified (NOS), tip lesion, or collapsing variants (COLL), versus secondary FSGS or cases without segmental sclerotic lesions where a diagnosis of MCD versus FSGS could not be established (undefined [UNDEF]) and compared the expression of DG, FSP1, and podocyte Wilms' tumor antigen (WT1).

Results: WT1 is markedly decreased in NOS versus normal and correlates with the extent of sclerosis. - and β-DG are maintained in most primary and secondary FSGS cases. In contrast, -DG is significantly decreased in UNDEF, supporting a diagnosis of MCD. Furthermore, follow-up shows remission or decreased proteinuria in four of six of these UNDEF cases in response to therapy. Interstitial FSP1 is numerically highest in COLL but is only rarely found in tubules or podocytes in any other forms of FSGS.

Conclusions: We conclude that increased FSP1 may be a marker of the aggressive course of collapsing FSGS. Furthermore, DG staining is a useful adjunct to assist in distinction of FSGS versus MCD in biopsies without defining lesions.

Design, setting, participants, & measurements: This is a single-center, retrospective analysis of the outcome of 46 patients who had systemic lupus erythematosus with nephritis and were treated with POCY between 1995 and 2006. POCY was given for 2 to 4 mo at a dosage of 1.0 to 1.5 mg/kg ideal body weight. After completing POCY, the patients received either azathioprine or mycophenolate mofetil.

Results: Median follow-up was 23.5 mo, and median duration of POCY was 4 mo (range 1 to 16 mo). Durable complete or partial remission of proteinuria was achieved in 32 (70%) patients, whereas 5 (11%) progressed to ESRD. Outcomes were comparable in black and white individuals. Adverse effects occurred in fewer than 10% of the cohort, and only four patients discontinued POCY.

Conclusions: These results suggest that sequential therapy of POCY followed by azathioprine or mycophenolate mofetil is comparable to IVCY regimens but that efficacy may not be affected by race.

Design, setting, participants, & measurements: We evaluated relationships of peripheral eosinophil count to degree of albumin excretion rate as well as to major cardiovascular risk factors, including age, BP, serum lipid concentration, and glycemic control (glycosylated hemoglobin); body mass index; current treatment for diabetes; smoking status; and presence of cardiovascular disease in 783 patients (416 men and 367 women) with type 2 diabetes.

Results: Log(eosinophil count) was positively associated with systolic BP (r = 0.124, P = 0.0108), serum triglyceride concentration (r = 0.108, P = 0.0284), and log(albumin excretion rate) (r = 0.301, P < 0.0001) in men; however, no association was found between log(eosinophil count) and log(albumin excretion rate) (r = 0.085, P = 0.1050) in women. Multivariate linear regression analysis demonstrated that log(eosinophil count) (β = 0.260, P < 0.0001), duration of diabetes (β = 0.203, P = 0.0003), glycosylated hemoglobin (β = 0.117, P = 0.0238), systolic BP (β = 0.205, P = 0.0001), and serum triglyceride concentration (β = 0.162, P = 0.0038) were independent determinants of log(albumin excretion rate) in men.

Conclusions: Allergic disorders may be associated with microalbuminuria in men with type 2 diabetes.

Design, setting, participants, & measurements: This was a case-control, single-center study of 1116 (243 with HIV infection and 873 without) consecutive ultrasound-guided biopsies from 1024 patients. The primary outcome was any major or minor complication. Major complications included biopsy-associated bleeding that required transfusion, angiography, or surgery; hypotension that required intervention; and death. Minor complications included development of a hematoma or gross hematuria. The odds of complication was assessed with logistic regression.

Results: Overall complication rates (8.6 versus 7.2%) did not significantly differ between HIV-infected and noninfected individuals. HIV-positive status did not predict complication. In the entire cohort, hepatitis C infection was associated with a 2.08 (95% confidence interval [CI] 1.47 to 2.93) increased odds of complication, and each 10,000-cells/mm³ decrease in prebiopsy platelet count a 1.05 (95% CI 1.02 to 1.08) increased odds of complication. In addition, prebiopsy hematocrit <30% and estimated GFR <30 ml/min per 1.73 m² were associated with major complication. Whereas the association of prebiopsy platelet count was not modified by HIV infection, hepatitis C/HIV co-infection was associated with a 5.71 (95% CI 1.89 to 17.2) increased odds of complication as compared with 1.27 (95% CI 0.73 to 2.19) in hepatitis C–positive/HIV-negative individuals.

Conclusions: Ultrasound-guided percutaneous kidney biopsy is a relatively safe, well-tolerated procedure in the HIV-infected population. HIV-infected individuals who are co-infected with hepatitis C seem to be at greatest risk.

Design, setting, participants, & measurements: Amikacin clearance was retrospectively analyzed in 161 neonates who received amikacin within the first 24 h of life. Using the MW/Pharm computer program, a population one-compartment model was calculated. The mean population pharmacokinetic parameters were individualized for each patient according to the maximum a posteriori Bayesian fitting method and provided the amikacin clearance.

Results: Our results show that birth weight z score and gestational age are correlated with the clearance of amikacin (partial correlation coefficient 0.159, P = 0.046, and 0.396, P < 0.001, respectively), after correction for other factors.

Conclusions: We conclude that renal clearance on the first day of life is lower in neonates with a lower gestational age and/or birth weight z score. This indicates that both prematurity and IUGR impair GFR on the first day of life.

Design, setting, participants, & measurements: A longitudinal cohort of 917 incident hemodialysis and peritoneal dialysis patients who completed the CHOICE Health Experience Questionnaire (CHEQ) participated in the study. Fatigue was assessed using the SF-36 vitality scale. Known predictors of fatigue including sociodemographic and psychosocial factors, dialysis-related factors, biochemical variables including inflammatory markers, comorbidities, and medications were used as covariates.

Results: A low vitality score was independently associated with white race, higher Index of Coexistent Disease score, higher body mass index, lack of physical exercise, antidepressant use, and higher C-reactive protein levels (CRP). A lower vitality score was strongly associated with lower SF-36 physical functioning, mental health, bodily pain scores, and decreased sleep quality (all P < 0.001) at baseline. Among surviving participants, higher serum creatinine at baseline was associated with preserved vitality at 1 yr. Patients with the highest baseline vitality scores were associated with longer survival (hazard ratio 0.75; 95% CI 0.58 to 0.96, P = 0.03).

Conclusions: The findings of this study demonstrate that ESRD patients experience profound levels of fatigue and elucidate its correlates. Also, the association of fatigue with survival may have significant implications for this population.

Design, setting, participants, & measurements: We retrospectively queried a prospective access database to analyze the outcomes of 175 tunneled dialysis catheters placed in the internal jugular vein, including 89 heparin-coated catheters and 86 noncoated catheters. The primary outcome was cumulative catheter survival, and the secondary outcome was infection-free catheter survival.

Results: The two patient groups were similar in demographics and clinical and catheter features. Catheter-related bacteremia occurred less frequently with heparin-coated catheters than with noncoated catheters (34 versus 60%, P < 0.001). Cumulative catheter survival was similar in heparin-coated and noncoated catheters (hazard ratio, 0.87; 95% confidence interval, 0.55 to 1.36; P = 0.53). On multiple variable survival analysis including catheter type, age, sex, diabetes, coronary artery disease, peripheral vascular disease, cerebrovascular disease, catheter location, and previous catheter, only catheter location predicted cumulative catheter survival (hazard ratio, 2.03; 95% CI, 1.27 to 3.25, with the right internal jugular location being the reference group, P = 0.003). The frequency of thrombolytic instillation was 1.8 per 1000 catheter-days in both groups.

Conclusions: Heparin coating decreases the frequency of catheter-related bacteremia but does not reduce the frequency of catheter malfunction.

Design, setting, participants, & measurements: Fifty-nine hemodialysis patients (17 female; age 58.4 ± 16.1 yr; body mass index 27.0 ± 5.4) were enrolled into a 12-mo, two-center, prospective cohort study. Deuterium concentration was measured in breath by flowing-afterglow mass spectrometry using a validated protocol ensuring full equilibration with the TBW; BIA was measured using a multifrequency, multisegmental device. Comorbidity was quantified by the Stoke score. Clinicians were blinded to body composition data.

Results: At baseline and 12 mo, there was an incremental discrepancy between TBW_BIA and TBW_D volumes such that greater comorbidity was associated with increasing overhydration. Forty-three patients who completed the study had no longitudinal differences in the prescribed or achieved postdialysis weights. In contrast, TBW_D increased without a change in TBW_BIA (mean difference –0.10 L). Changes in TBW and lean body mass differed according to baseline comorbidity; without comorbidity, BIA also identified an increase in TBW and lean body mass, whereas with increasing comorbid burden, BIA failed to demonstrate increases in tissue hydration identified by TBW_D.

Conclusions: Combined near-patient measurements of absolute and BIA-estimated TBW are achievable in a dialysis facility by identifying changes in body composition not fully appreciated by routine assessment. BIA underestimates tissue overhydration that is associated with comorbidity, resulting in reduced sensitivity to longitudinal increases during a 12-mo period.

Design, setting, participants, & measurements: This was a randomized, double-blind, perspective control study. Stable prevalent continuous ambulatory peritoneal dialysis (CAPD) patients were randomized to either 7.5% icodextrin (ICO) or 2.5% glucose (GLU) solution for 4 wk. Peritoneal membrane function was measured to define PET category in baseline. Creatinine clearance (Ccr), urea nitrogen clearance (C_BUN), ultrafiltration (UF) during the long night dwell, dialysate, and metabolic biomarkers were measured at baseline, 2, and 4 wk. UF, Ccr, and C_BUN were compared among different PET categories.

Results: A total of 201 CAPD patients were enrolled in the study. There were no baseline differences between the groups. Following 2 and 4 wk of therapy, Ccr, C_BUN, and UF were all significantly higher in the ICO versus the GLU group. Additionally, switching to ICO resulted in a significant increase in UF in high, high-average, and low-average transporters as compared with baseline. The extent of increased UF was more obvious in higher transporters. Blood cholesterol level in the ICO group decreased significantly than that in the GLU group.

Conclusion: Compared with glucose-based solution, 7.5% icodextrin significantly improved UF and small solute clearance, even in patients with low-average peritoneal transport.

Design, settings, participants & measurements: In 1094 participants in the African-American Study of Kidney Disease and Hypertension (AASK) database, the associations of serum alkaline phosphatase with mortality and cardiovascular events were examined in Cox models.

Results: The mean (±SD) age was 54 ± 11 yr, and 61% were men. The median alkaline phosphatase was 80 IU/L, and interquartile range was 66 to 97 IU/L. The mean follow-up was 4.6 yr. There were 105 (9.6%) all-cause deaths and 149 (13.6%) cardiovascular events. Each doubling of serum alkaline phosphatase was significantly associated with increased hazard [hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.08 –2.36] of all-cause mortality adjusted for demographics, drug and blood pressure groups, and comorbidity. With further adjustment for liver function tests as well as serum calcium and phosphorus, each doubling of serum alkaline phosphatase remained significantly associated with increased mortality (HR 1.55, 95% CI 1.03 to 2.33). Serum alkaline phosphatase was not significantly associated with increased risk of cardiovascular events.

Conclusions: Independent of liver function tests and serum calcium and phosphorus, higher levels of serum alkaline phosphatase are associated with increased mortality in the CKD population. Further studies are warranted to identify the potential mechanisms for this association.

Design, setting, participants, & measurements: Worsening renal function was defined as a 25% or more decrease in estimated GFR (eGFR) over a 1-mo period in patients after a non-ST or ST elevation acute coronary syndromes participating in the Aggrastat-to-Zocor Trial; this occurred in 5% of the 3795 participants.

Results: A baseline C-reactive protein (CRP) in the fourth quartile was a significant predictor of developing worsening renal function (odds ratio, 2.48; 95% confidence interval, 1.49, 4.14). After adjusting for baseline CRP and eGFR, worsening renal function remained a strong multivariate predictor for the combined cardiovascular composite of CV death, recurrent myocardial infarction (MI), heart failure or stroke (hazard ratio, 1.6; 95% confidence interval, 1.1, 2.3).

Conclusions: Patients with an early decline in renal function after an acute coronary syndrome are at a significant increased risk for recurrent cardiovascular events. CRP is an independent predictor for subsequent decline in renal function and reinforces the idea that inflammation may be related to the pathophysiology of progressive renal disease.

Design, setting, participants, & measurements: Comorbidity data were abstracted from the medical records of Dialysis Outcomes and Practice Pattern Study (DOPPS) I, II, and III participants using a standardized questionnaire. Models that were composed of different combinations of comorbid conditions and case-mix factors were compared for explained variance (R²) and discrimination (c statistic).

Results: Seventeen comorbid conditions account for 96% of the total explained variance that would result if 45 comorbidities that were expected to be predictive of survival were added to a demographics-adjusted survival model. These conditions together had more discriminatory power (c statistic 0.67) than age alone (0.63) or serum albumin (0.60) and were equivalent to a combination of routine laboratory and clinical parameters (0.67). The strength of association of the individual comorbidities lessened when laboratory/clinical parameters were added, but all remained significant. The total R² of a model adjusted for demographics and laboratory/clinical parameters increased from 0.13 to 0.17 upon addition of comorbidity.

Conclusions: A relatively small list of comorbid conditions provides equivalent discrimination and explained variance for survival as a more extensive characterization of comorbidity. Comorbidity adds to the survival model a modest amount of independent prognostic information that cannot be substituted by clinical/laboratory parameters.