Design, setting, participants, and measurements: MEDLINE, EMBASE, HuGEnet, SCOPUS, and Web of Science were searched for articles from 1950 to Dec 2007. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality via an aggregate scoring system.

Results: The 16 included studies were of cohort or case-cohort design and investigated 35 polymorphisms in 21 genes in association with AKI. Fifteen gene-gene interactions were also investigated in four separate studies. Study populations were primarily premature infants or adults who were critically ill or postcardiac bypass patients. Among the studies, five different definitions of AKI were used. Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence. The mean quality score of 5.8/10 (range four to nine), heterogeneity in the studies, and the dearth of studies precluded additional meta-analysis of the results.

Conclusions: Current association studies are unable to provide definitive evidence linking genetic variation to AKI. Future success will require a narrow consensus definition of AKI, rigorous epidemiologic techniques, and a shift from a priori hypothesis-driven to genome-wide association studies.

Design, setting, participants, & measurements: We conducted a collaborative meta-analysis with data provided by the main authors of identified trials to estimate the effectiveness of early angiography in patients with CKD. The Cochrane, Medline, and EMBASE databases were searched to identify randomized trials that compared invasive and conservative strategies in patients with unstable angina or non-ST MI. Pooled risks ratios were estimated using data from enrolled patients with estimated GFR <60 ml/min per 1.73 m².

Results: Five randomized trials that enrolled 1453 patients with CKD were included. An early invasive strategy was associated with nonsignificant reductions in all-cause mortality, nonfatal MI, and a composite of death or nonfatal MI. The invasive strategy significantly reduced rehospitalization.

Conclusions: This collaborative study suggests that the benefits of an early invasive strategy are preserved in patients with CKD and that an early invasive approach reduces the risk for rehospitalization and is associated with trends of reduction in the risk for death and nonfatal re-infarction in patients with CKD. Coronary angiography should be considered for patients who have CKD and are admitted with non–ST elevation acute coronary syndromes.

Design, setting, participants, & measurements: This was an observational, cross-sectional study of 158 prevalent patients (90 CAPD, 68 CCPD). Demographic data, blood work, and 24-h dialysate and urine samples were collected from all participants between January 2004 and July 2006. They subsequently underwent assessment of ECFV by multifrequency bioimpedance spectroscopy analysis. Multivariate analysis was used to determine the relationship between peritoneal dialysis modality and ECFV. Potential cofounders including age, comorbidity, time on dialysis, residual renal function, and icodextrin use were identified a priori.

Results: There were no differences in BP, use of antihypertensive medications, or the presence of peripheral edema between CAPD and CCPD patients. Similarly, there was no difference in the ratio of ECFV to total body water between CAPD (51.8%) and CCPD (51.9%) patients (P = 0.929).

Conclusions: There is no difference in BP, sodium removal, or volume control in patients who use a contemporary approach to CCPD that uses fewer night cycles and liberalizes the use of icodextrin when compared with CAPD.

Design, setting, participants, & measurements: This study reports the first measurements of bioactive serum hepcidin using a novel competitive ELISA in 48 pediatric (PCKD2–4) and 32 adult (ACKD2–4) patients with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD (PCKD5D) on peritoneal dialysis.

Results: When compared with their respective controls (pediatric median = 25.3 ng/ml, adult = 72.9 ng/ml), hepcidin was significantly increased in PCKD2–4 (127.3 ng/ml), ACKD2–4 (269.9 ng/ml), and PCKD5D (652.4 ng/ml). Multivariate regression analysis was used to assess the relationship between hepcidin and indicators of anemia, iron status, inflammation, and renal function. In PCKD2–4 (R² = 0.57), only ferritin correlated with hepcidin. In ACKD2–4 (R² = 0.78), ferritin and soluble transferrin receptor were associated with hepcidin, whereas GFR was inversely correlated. In PCKD5D (R² = 0.52), percent iron saturation and ferritin were predictors of hepcidin. In a multivariate analysis that incorporated all three groups (R² = 0.6), hepcidin was predicted by ferritin, C-reactive protein, and whether the patient had stage 5D versus stages 2 to 4 CKD.

Conclusions: These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance.

Design, setting, participants, & measurements: Patients with ESRD and subjects with advanced CKD were enrolled. Patients’ symptoms, depression, and quality of life were assessed using the Dialysis Symptom Index (DSI), Patient Health Questionnaire-9 (PHQ-9), and Short Form 36 (SF-36), respectively, and these health domains were compared between patient groups.

Results: Ninety patients with ESRD and 87 with CKD were enrolled. There were no differences in the overall number of symptoms or in the total DSI symptom-severity score. Median scores on the PHQ-9 were similar, as was the proportion of patients with PHQ-9 scores >9. SF-36 Physical Component Summary scores were comparable, as were SF-36 Mental Component Summary scores.

Conclusions: The burden of symptoms, prevalence of depression, and low quality of life are comparable in patients with ESRD and advanced CKD. Given the widely recognized impairments in these domains in ESRD, findings of this study underscore the substantial decrements in the physical and psychologic well-being of patients with CKD.

Design, setting, participants, & measurements: We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal survival probabilities were compared with those of a concurrent cohort with idiopathic NS.

Results: Patients with a single mutation in NPHS1 received a diagnosis before those with potentially nongenetic NS and had a good response to therapies. Renal function was normal in all cases. For NPHS2, six patients had single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q variant. Age at diagnosis and the response to drugs were comparable in all NS subgroups. Overall, they had similar renal survival probabilities as non-NPHS1/NPHS2 cases (log-rank ² 0.84, P = 0.656) that decreased in presence of resistance to therapy (P < 0.001) and in cases with renal lesions of glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that the only significant predictor of dialysis was resistance to therapy.

Conclusions: Our data indicate that single mutation or variant in NPHS1 and NPHS2 does not modify the outcome of primary NS. These patients should be treated following consolidated schemes and have good chances for a good long-term outcome.

Design, setting, participants, & measurements: All native renal biopsies (n = 235 including 106 men, 129 women) performed in patients aged ≥80 yr over a 3.67-yr period were retrospectively identified. Results were compared with a control group of 264 patients aged 60 to 61 who were biopsied over the same period.

Results: The indications for biopsy were acute kidney injury (AKI) in 46.4%, chronic-progressive kidney injury in 23.8%, nephrotic syndrome (NS) in 13.2%, NS with AKI in 9.4%, and isolated proteinuria in 5.5%. Pauci-immune GN was the most frequent diagnosis (19%), followed by focal segmental glomerulosclerosis secondary to hypertension (7.6%), hypertensive nephrosclerosis (7.1%), IgA nephropathy (7.1%) and membranous nephropathy (7.1%). Comparison with the control group showed pauci-immune GN to be more frequent (P < 0.001) and diabetic glomerulosclerosis (P < 0.001) and membranous nephropathy (P < 0.05) less frequent in the very elderly. Diagnostic information had the potential to modify treatment in 67% of biopsies from the very elderly, particularly in those with AKI or NS.

Conclusions: Renal biopsy in very elderly patients is a valuable diagnostic tool that should be offered in clinical settings with maximal potential benefit. Advanced age per se should no longer be considered a contraindication to renal biopsy.

Design, setting, participants, and measurements: Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m²). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal.

Results: After rituximab, proteinuria decreased significantly (2.5 ± 0,76 basal versus 0.85 ± 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 ± 15 basal to 106.4 ± 20 at 3 mo with a mean increase of 15.3% [range 0–20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission.

Conclusions: In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.

Design, setting, participants, & measurements: Two hundred and thirty-three prevalent, chronic dialysis patients from three units in different geographic areas in the United States underwent a single, cross-sectional assessment of total daily pill burden and that from phosphate binders. HR-QOL, adherence to phosphate binders, and serum phosphorus levels were the three main outcome measures studied.

Results: The median daily pill burden was 19; in one-quarter of subjects, it exceeded 25 pills/d. Higher pill burden was independently associated with lower physical component summary scale scores on HR-QOL on both univariate and multivariate analyses. Phosphate binders accounted for about one-half of the daily pill burden; 62% of the participants were nonadherent. There was a modest relationship between pill burden from phosphate binders and adherence and serum phosphorus levels; these associations persisted on multivariate analyses. There was no relationship between adherence and serum phosphorus levels.

Conclusions: The daily pill burden in dialysis patients is one of the highest reported to date in any chronic disease state. Higher pill burden is associated with lower HR-QOL. There are many reasons for uncontrolled serum phosphorus levels; increasing the number of prescribed pills does not seem to improve control and may come at the cost of poorer HR-QOL.

Design, settings, participants, & measurements: Patients who ever had LOH for three or more consecutive sessions were identified (n = 146). Indices of urea reduction ratio (URR), anemia, hyperphosphatemia, and predialysis BP (BP) control in a subgroup of all patients on LOH for at least 1 yr since 2004 were compared with age, sex, and diabetes-matched controls undergoing conventional duration HD.

Results: The mean age at the time of starting LOH was 51.8 yr and 74.7% started with a functioning arteriovenous fistula. Median duration of continuous LOH was 1.6 yr. Of those no longer on LOH, only 33.3% reverted to conventional hours HD (mean duration LOH 2.2 yr). When comparing LOH and conventional HD cohorts, there was increased URR and mean hemoglobin with a trend toward lower mean erythropoietin index. There was a trend toward fewer phosphate binder tablets but no difference in mean serum phosphate, BP, or number of prescribed antihypertensive medicines.

Conclusions: LOH is a well tolerated hemodialysis option, associated with improved URR and better control of anemia.

Design, setting, participants, & measurements: We retrospectively queried a prospective, computerized vascular access database to identify 40 hemodialysis patients with catheter-related candidemia. All patients underwent treatment with antifungal medications for 2 wk, in conjunction with guidewire catheter exchange or catheter removal with delayed replacement. The primary outcomes were major complications, recurrent candidemia, and patient survival.

Results: Candidemia represented approximately 2% of all cases of catheter-related bloodstream infections. Of the 40 patients with candidemia, 27 underwent guidewire catheter exchange and 13 had prompt catheter removal with delayed replacement. The two treatment groups were similar in demographic, clinical, and catheter characteristics. Only 1 (2.5%) patient developed a serious complication (endophthalmitis). Recurrence of candidemia within 3 mo was observed in 15% of each treatment group. Patient survival at 6 mo was similar in both groups.

Conclusions: Catheter-related candidemia is rare in hemodialysis patients and has a low complication rate. Catheter exchange over a guidewire in conjunction with antifungal therapy is an effective and safe treatment regimen.

Design, setting, participants, & measurements: We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured.

Results: Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P = 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant.

Conclusions: An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.

Design, settings, participants, & methods: The Modification of Diet in Renal Disease Study was a randomized, controlled trial conducted between 1989 and 1993. We measured ADMA in frozen samples collected at baseline (n = 820) and obtained survival status, up to December 31, 2000, from the National Death Index. We examined the relationship of ADMA with prevalent CVD and performed multivariable Cox models to examine the relationship of ADMA with all-cause and CVD mortality.

Results: Mean (SD) age was 52 (12) yr, GFR was 32 ± 12 ml/min per 1.73 m², and ADMA was 0.70 ± 0.25 µmol/L. A 1-SD increase in ADMA was associated with a 31% increased odds of prevalent CVD in an adjusted logistic regression model. During the 10-yr follow-up period, 202 (25%) participants died of any cause, 122 (15%) from CVD, and 545 (66%) reached kidney failure. In multivariable Cox models, a 1-SD increase in ADMA was associated with a 9% increased risk for all-cause and 19% increased risk for CVD mortality.

Conclusions: In this cohort of patients with predominantly nondiabetic, stages 3 to 4 chronic kidney disease, there was a strong association of ADMA with prevalent CVD and a modest association with all-cause and CVD mortality.

Design, setting, participants, & measurements: This was a retrospective cohort analysis of 243,222 patients who had 2,040,206 glucose measurements and were cared for at the Veterans Health Administration. CKD was defined as an estimated GFR of <60 ml/min per 1.73 m². Hypoglycemia was set at <70 mg/dl. Mortality was measured 1 day after glucose measurement.

Results: The incidence of hypoglycemia was higher in patients with CKD versus without CKD. Among patients with diabetes, the rate was 10.72 versus 5.33 per 100 patient-months and among patients without diabetes was 3.46 versus 2.23 per 100 patient-months, for CKD versus no CKD, respectively. The odds of 1-d mortality were increased at all levels of hypoglycemia but attenuated in CKD versus no CKD. Adjusted odds ratios for 1-d mortality that were associated with glucose values of <50, 50 to 59, and 60 to 69 mg/dl, respectively, versus glucose of ≥70 mg/dl were 6.09, 4.10, and 1.85 for inpatient records from patients with CKD; 9.95, 3.79, and 2.54 for inpatients records from patients without CKD; 6.84, 3.28, and 3.98 for outpatient records from patients with CKD; and 13.28, 7.36, and 4.34 for outpatient records from patients without CKD.

Conclusions: CKD is a risk for hypoglycemia, with or without diabetes. The excessive mortality associated with hypoglycemia makes this complication a significant threat to patient safety in CKD.

Design, setting, participants & measurements: One hundred forty CKD patients (85 men, mean age 67 ± 12 yr; CKD stages 2 [8%], 3 [26%], 4 [26%], 5 [7%], and 5D [(33%]) were allocated for a prospective study. Serum levels of 25D and 1,25-dihydroxyvitamin D, aortic calcification score, and pulse wave velocity (PWV) were evaluated.

Results: There was a high prevalence of vitamin D deficiency (42%) and insufficiency (34%). Patients with 25D ≤ 16.7 ng/ml (median) had a significantly lower survival rate than patients with 25D >16.7 ng/ml (mean follow-up, 605 ± 217 d; range, 10 to 889; P = 0.05). Multivariate adjustments (included age, gender, diabetes, arterial pressure, CKD stage, phosphate, albumin, hemoglobin, aortic calcification score and PWV) confirmed 25D level as an independent predictor of all-cause mortality.

Conclusions: Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort. Low 25D levels affected mortality independently of vascular calcification and stiffness, suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored.