Design, setting, participants, & measurements: The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed for 98 patients who had IgAN with an estimated GFR of ≥60 ml/min per 1.73 m2 at biopsy (87 ml/min per 1.73 m2 on average). \
Results: The individual value of GD in biopsy ranged from 1.2 to 8.1/mm2 (i.e., approximately a seven-fold variation), and the GD showed a close inverse correlation with mean glomerular volume. Among the various clinicopathologic factors involved, both a cellular/fibrocellular crescent and the GD were found to be significant predictors of progression in multivariate analyses. A low GD in the biopsy specimens was frequently associated with a steeper slope of the renal function and a synergistically enhanced risk for progression with the presence of cellular/fibrocellular crescent. The renal function, proteinuria, degrees of glomerulosclerosis, and interstitial fibrosis at biopsy were not independent predictors of the prognosis in these patients. \
Conclusions: A strong predictive relationship of low GD with progression observed in this study suggests that GD may serve as an early histopathologic marker of long-term renal prognosis in IgAN.
]]>Design, setting, participants, & measurements: This was a cross-sectional study of 100 Tx and 50 WL patients who underwent one-night polysomnography (SLeep disorders Evaluation in Patients after kidney Transplantation [SLEPT] Study). Sociodemographic information and data about medication, comorbidity, and laboratory parameters were collected. \
Results: The prevalence of mild (apnea-hypopnea index [AHI] ≥5/h and <15/h), moderate (AHI ≥15/h and <30/h), and severe OSA (AHI ≥30/h) was 18, 11, and 14% in the Tx group and 28, 16, and 10% in the WL group, respectively. The AHI was significantly correlated with age ( = 0.34), body mass index ( = 0.45), neck circumference ( = 0.4), abdominal circumference ( = 0.51), and hemoglobin ( = 0.24) in the Tx group. The proportion of Tx patients who were treated with three or more antihypertensive drugs was significantly higher in the OSA group (56 versus 31%; P = 0.022). Despite taking significantly more antihypertensive drugs, the average systolic BP was still higher in patients with versus without OSA (147 ± 21 versus 139 ± 18 mmHg; P = 0.059). \
Conclusions: The prevalence of OSA is similar in Tx and WL patients and it may contribute to presence of hypertension in patients who receive a Tx.
]]>Design, setting, participants, & measurements: DCOR trial participants were linked to the Centers for Medicare & Medicaid Services ESRD database. Medicare costs for 1895 dosed Medicare-primary-payer participants were evaluated. Phosphate binder costs were incorporated. Costs were indexed to 2001 (study base year). Sensitivity analyses were performed with randomized participants, two follow-up periods, and 2004 as index year.
Results: Inflation-adjusted Medicare per member per month (PMPM) costs were lower for sevelamer-treated than for calcium-treated participants by a mean differential of $199 PMPM (mean, $5236 versus $5435; median, $4653 versus $4933), mainly because of lower inpatient costs for the sevelamer group (mean, $1461 versus $1644; median, $909 versus $1144). However, after phosphate binder costs were incorporated, costs trended lower for calcium-treated than for sevelamer-treated patients (differential −$81, 95% confidence interval −$321 to $157 PMPM, using average wholesale price; −$25, −$256 to $213 PMPM, using wholesale acquisition cost).
Conclusions: Sevelamer reduced inpatient Medicare costs compared with calcium binders. However, when binder costs were added, overall PMPM costs favored calcium-treated over sevelamer-treated participants.
]]>Design, setting, participants, & measurements: Mortality, treatment modalities, and growth were reanalyzed 9.9 yr later. \
Results: Of the 101 patients, 28 died and three were lost to follow-up during 13.90 yr (range 0.03 to 22.90 yr). One-, 2-, 5-, 10-, 15-, 20-, and 22-yr survivals were 87, 81, 77, 75, 73, 72, and 64%, respectively. Fifty-one children had comorbidities. Sixty-six percent were tube fed for 1.7 yr (range 0.1 to 6.9 yr), 37% had a gastrostomy, and 13% had a Nissen fundoplication. Mean height SD score (SD) was −0.42 (2.33) at birth (n = 40), −2.07 (1.34) at 0.5 (n = 62), −1.93 (1.38) at 1 (n = 72), −1.14 (1.14) at 5 (n = 67), −1.04 (1.15) at 10 (n = 62), −1.84 (1.32) at 15 (n = 40), and −1.68 (1.52) at age ≥18 yr (n = 32). Comorbidities adversely influenced growth (P < 0.01) and final height (P = 0.02): Mean height SD score (SD) was −1.16 (1.38) in otherwise normal adults. \
Conclusions: Growth and final height in infants with severe chronic kidney disease are influenced by comorbidity. Intensive feeding and early transplantation resulted in a mean adult height within the normal range in patients without comorbidities. Overall mortality is comparable to that of older children.
]]>Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). \
Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. \
Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes.
]]>Design, setting, participants, & measurements: In a retrospective study, we analyzed the outcome of infants who had chronic kidney disease and started RRT within their first year of life. Between 1997 and 2008, all 29 infants who were younger than 1 yr, had end-stage renal failure, and underwent RRT (dialysis or transplantation) at Hannover Medical School were analyzed for up to 12 yr. \
Results: Twenty-seven of 29 infants with chronic kidney disease received peritoneal dialysis, starting at a mean age of 112 d; two children received preemptive renal transplantation (RTx). During follow-up, 21 of 29 children survived with RTx. The 5-yr patient and graft survival rate after RTx was 95.5%. Six of 29 children died, one with a functioning graft and five while on peritoneal dialysis. The main causes of death were severe cardiovascular and cerebral comorbidities. The mean GFR at last follow-up of patients who underwent RTx (mean time after RTx 5.1 yr) was 63.2 ml/min per 1.73 m2. \
Conclusions: RRT in infants who are younger than 1 year offers excellent chances of survival and should be offered to all infants who do not have severe, life-limiting extrarenal comorbidity. Contrary to previous observations, the long-term outcome of infants may be comparable to that of older children who undergo RRT.
]]>Design, setting, participants, & measurements: Predialysis serum β2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in β2M were analyzed using multivariable linear regression models. \
Results: Mean serum β2M levels decreased from 29.5 ± 0.8 (±SEM) at baseline to 24.3 ± 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 ± 0.9 to 34.4 ± 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient −7.7 mg/L, 95% confidence interval −9.5 to −5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, β2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The β2M decrease was not related to convective volume. \
Conclusions: This study demonstrated effective lowering of β2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on β2M decrease appears limited, possibly because of resistance to β2M transfer between body compartments.
]]>Design, setting, participants, & measurements: Medline on OVID was searched in November 2008, with MESH and free terms on pregnancy and chronic kidney disease or dialysis; limits were human subjects and English-language articles. Case reports were excluded to minimize publication bias. The final selection and extraction of data were performed in duplicate.
Results: From 2840 references, 241 full-text articles were retrieved; eight fulfilled the selection criteria, and two were added from reference lists. In the 10 studies (nine of 10 monocentric), 90 pregnancies were observed in 78 patients (range of cases five to 15). The studies were heterogeneous for definition of outcomes, duration (2 to 16 yr), period (1988 through 1998 to 2000 through 2006), age (25 to 35 yr), and support and dialysis therapy. Daily dialysis was frequently used; type of treatment, membranes, and flows varied widely. Hypertension and anemia were frequent concerns for the mothers. Intrauterine deaths, hydramnios, and small-for-gestational-age or preterm infants were frequent. The possibility of a healthy offspring ranged from 50 to 100% (overall 76.25%).
Conclusions: Evidence on pregnancy in dialysis is heterogeneous; however, the growing number of reports worldwide and the improving results suggest that we should reconsider our counseling policy, which only rarely includes pregnancy in dialysis patients.
]]>Design, setting, participants, & measurements: Tissue AGE were measured in 115 established dialysis patients (62 HD and 53 PD) using a cutaneous AF device (AGE Reader; DiagnOptics). Values were compared with an age-matched non–chronic kidney disease database. Review of all previous PD solution delivery/prescription data determined PD glucose exposure.
Results: PD patients were similar in age to HD patients but had a shorter dialysis vintage. There were no differences in ischemic heart disease or smoking history, statin or angiotensin-converting enzyme inhibitor (ACEi) use, lipids, biochemistry, or prevalence of diabetes. More than 90% of both groups had met current dialysis adequacy targets. Skin AF values in PD and HD patients were similar and strongly correlated with historical PD glucose exposure. Skin AF correlated with age in both groups but with dialysis vintage only in PD patients
Conclusions: Cumulative metabolic stress and transient hyperglycemia results in grossly elevated levels of tissue AGE in dialysis patients. In PD patients, this high level of AGE deposition is associated with historical glucose exposure. This observation provides a previously unappreciated potential link between PD exposure to glucose and systemic cardiovascular disease.
]]>Design, setting, participants, & measurements: We assessed intact FGF23 levels in 91 subjects over the course of the ACHIEVE trial, which was designed to compare escalating doses of Cinacalcet plus fixed low-dose calcitriol analogs (Cinaclcet-D) with titration of calcitriol analogs alone (Flex-D) to suppress parathyroid hormone. Between-group and within-group changes in log-transformed FGF23 levels were analyzed. Factors associated with change in FGF23 were assessed using a multiple regression model.
Results: Intact FGF23 levels were markedly elevated in subjects at baseline. A statistically significant difference in percent change in log FGF23 levels was observed between treatment groups (P < 0.002). The Cinacalcet-D group had a significant decrease in percent change in log FGF23 levels (corrected P = 0.021), whereas FGF23 levels trended toward an increase in the Flex-D group. Change in FGF23 level was significantly associated with changes in levels of phosphate (P < 0.0001) and calcium (P = 0.0002) but not parathyroid hormone.
Conclusions: Treatment with Cinacalcet plus low-dose calcitriol analogs results in lower FGF23 levels compared with a treatment regimen using calcitriol analogs alone in ESRD. The mechanisms underlying the differential effects of these treatment regimens on FGF23 levels and the clinical impact of these changes on FGF23 remain to be defined.
]]>Design, setting, participants, & measurements: This is a prospective cohort analysis from the Spokane Heart Study, a long-term observational study of community-dwelling adults who were assessed every 2 yr for CAC (electron-beam computed tomography), CVD risk factors, and laboratory testing. Estimated GFR (eGFR) was determined by the reexpressed Modification of Diet in Renal Disease equation.
Results: CAC was present in 28% (245 of 883) at baseline. After 6 yr, new-onset CAC developed in 33% (122 of 371); severity increased from a median CAC score of 38 to 152 in those with baseline CAC. Neither eGFR (101 ± 34 versus 104 ± 31 ml/min per 1.73 m2, respectively) nor serum phosphorus (3.25 ± 0.49 versus 3.29 ± 0.48 mg/dl, respectively) differed by CAC presence or absence at baseline; however, multivariate models (generalized estimating equations for incidence and prevalence) revealed that independent predictors of CAC over time were greater baseline CAC scores, higher serum phosphorus levels, lower eGFR levels, and traditional CVD risk factors. Each 1-mg/dl increase in phosphorus imparted odds ratios for CAC of 1.61 (incidence) and 1.54 (prevalence), risks comparable to traditional CVD risk factors.
Conclusions: CAC becomes more frequent and severe over time. Higher levels of serum phosphorus and reduced kidney function independently predicted CAC.
]]>Design, setting, participants, & measurements: Patients who were admitted for an ACS in eight participating hospitals were stratified into three groups according to estimated creatinine clearance (CrC): less than 45 ml/min, 45 to 60 ml/min, and reference >60 ml/min.
Results: During hospitalization, uses of reperfusion therapy in tertiary care centers [difference between CrC ≤45 ml/min and reference group (): 4%, 95% confidence interval (CI): (−13%, 21%)] and systemic anticoagulation [: 0%, CI (−5%, 5%)] were similar in the three groups. Coronary angiography was performed less often in patients with lower CrC [: −16%, CI: (−31%, −1%)]. At discharge, nearly all patients received either an antiplatelet agent or warfarin regardless of CrC [: −1%, CI: (−3%, 1%)]. Discharge use of angiotensin converting enzyme (ACE) inhibitors or angiotensin-receptor blockers was comparable [: 7%, CI: (−1%, 15%)]. β-blockers [: −9%, CI: (−17%, −1%)] and lipid-lowering drugs (LLDs) [: −7%, CI: (−13%, −1%)] were used less frequently in patients with lower CrC. In multivariate analyses, decreased CrC predicted lower coronary angiography and LLD use, but not lower β-blocker use at discharge.
Conclusions: These results suggest that in patients with ACS, the extent of undertreatment due to chronic kidney disease is less than reported previously, which is partially explained by more complete adjustment for cotreatments/comorbidities.
]]>Design, setting, participants, & measurements: Eighty-nine diabetics with mild to moderate proteinuria and normal to mildly reduced GFR who were normotensive, nondyslipidemic, and cardiovascular-events free were enrolled. None of the patients was taking metformin or renin-angiotensin system blockers.
Results: FMD was inversely related with Hb levels. Furthermore, there was an inverse link between proteinuria and FMD. However, further analysis of this association showed that the FMD-proteinuria link was confined to patients with proteinuria exceeding 150 mg/d, while no such association existed in patients with proteinuria <150 mg/d. Adjustment of the Hb-FMD relationship for pertinent Framingham risk factors, proteinuria, homeostasis model assessment (HOMA) index, and GFR levels had a modest influence on this association, which remained significant.
Conclusions: Endothelial function is inversely associated with Hb levels in diabetic patients with stage 1 to 2 CKD, and proteinuria is an effect modifier of this association. Overall, the observations of this study generate the hypothesis that proteinuria exposes a situation wherein Hb may limit the endothelium-mediated vasoregulation in diabetes.
]]>Design, setting, participants, & measurements: All patients receiving IVIG for desensitization or for treatment of AMR were monitored for evidence of acute anemia and hemolysis. Markers of hemolysis, including direct antiglobulin tests, were recorded. Five different IVIG products were tested for isohemagglutinin titers.
Results: There were 18 cases of IH in 16 patients. All identified cases received the IVIG product Gamunex, Gammagard liquid, or Privigen. All patients developing hemolysis were non-O blood types. Isohemagglutinin titers ranged from 1:2 to 1:64 in the various IVIG products, with higher titers noted in the liquid, nonlyophilized products.
Conclusions: Acute IH is a significant complication of high-dose IVIG infusion. Identified risk factors include non-O blood type of the recipient and administration of liquid IVIG preparations with high titer anti-A/B IgG antibodies. We recommend monitoring hemoglobin 48 to 72 h after IVIG infusion. If the hemoglobin decreases, a hemolytic work-up is recommended. Hemolysis could be avoided in at risk patients by choosing a low titer product. However, other complications such as acute renal failure or thrombosis may be seen because the low titer products are usually hyperosmotic.
]]>Design, setting, participants, & measurements: Autopsy subjects known to have coronary artery disease and a wide range of kidney function were studied. Patients without CKD were classified into five groups depending on estimated GFR (eGFR) and proteinuria: eGFR ≥60 ml/min/1.73 m2 without proteinuria; CKD1/2: eGFR ≥60 ml/min/1.73 m2 with proteinuria; CKD3: 60 ml/min/1.73 m2 >eGFR ≥30 ml/min/1.73 m2; CKD4/5: eGFR <30 ml/min/1.73 m2; and CKD5D: on hemodialysis. Intimal and medial calcification of the coronary arteries was evaluated. Risk factors for CVD and uremia were identified as relevant to CAC using logistic regression analysis.
Results: Intimal calcification of plaques was present in all groups, but was most frequent and severe in the CKD5D group and less so in the CKD4/5 and CKD3 groups. Risk factors included luminal stenosis, age, smoking, diabetes, calcium-phosphorus product, inflammation, and kidney function. Medial calcification was seen in a small number of CKD4/5 and CKD5D groups. Risk factors were use of calcium-containing phosphate binders, hemodialysis treatment, and duration.
Conclusions: It was concluded that CAC was present in the intimal plaque of both nonrenal and renal patients. Renal function and traditional risks were linked to initimal calcification. Medial calcification occurred only in CKD patients.
]]>Design, setting, participants, & measurements: We explored HGFIN expression in monocytes and monocyte-derived macrophages in 21 stable hemodialysis patients and 22 control subjects. \
Results: Dialysis patients exhibited marked upregulation of colony-stimulating factor and IL-6 and significant downregulation of IL-10 in intact monocytes and transformed macrophages. HGFIN expression in intact monocytes was negligible in control subjects but conspicuously elevated (8.6-fold) in dialysis patients. As expected, in vitro monocyte-to-macrophage transformation resulted in marked upregulation of HGFIN in cells obtained from both groups but much more so in dialysis patients (17.5-fold higher). Upregulation of HGFIN and inflammatory cytokines in the uremic monocyte-derived macrophages occurred when grown in the presence of either normal or uremic serum, suggesting the enduring effect of the in vivo uremic milieu on monocyte/macrophage phenotype and function. \
Conclusions: Uremic macrophages exhibit increased HGFIN gene and protein expression and heightened expression of proinflammatory and a suppressed expression of anti-inflammatory cytokines. Further studies are needed to determine the role of heightened monocyte/macrophage HGFIN expression in the pathogenesis of ESRD-induced inflammation and vascular and soft tissue calcification.
]]>Design, setting, participants, & measurements: In an observational study in 75 maintenance hemodialysis patients, we studied agreement between indoxyl sulfate and p-cresyl sulfate serum concentrations, dialytic reduction rates, and dialytic clearances. Concentrations were determined by HPLC. Dialytic clearances were determined from total spent dialysate collections. In vitro spiking experiments were performed to explore protein binding characteristics.
Results: Indoxyl sulfate and p-cresyl sulfate total serum concentrations were not related (r = 0.02, P = 0.9), whereas free serum concentrations were only moderately related (r = 0.53, P < 0.001). Indoxyl sulfate and p-cresyl sulfate share the same albumin binding site, for which they are competitive binding inhibitors. Intriguingly, indoxyl sulfate and p-cresyl sulfate reduction rates (r = 0.91, P < 0.001) and dialytic clearances (r = 0.97, P < 0.001) correlated tightly.
Conclusions: Indoxyl sulfate and p-cresyl sulfate serum concentrations are not associated, suggesting different metabolic pathways. Indoxyl sulfate and p-cresyl sulfate are both valid markers to monitor behavior of protein-bound solutes during dialysis. Finally, they are competitive binding inhibitors for the same albumin binding site.
]]>Design and setting: This retrospective analysis included 482 patients with stage IV/V CKD seen in West London predialysis clinics from 2004 to 2007. Seventy-six of 482 (15.8%) patients considered as potential transplant recipients met the authors’ criteria for coronary angiography. Modification of Diet in Renal Disease (MDRD) GFR measurements were recorded for the 12 mo preceding and 12 mo following CA unless a defined endpoint was reached (transplantation, dialysis, or death).
Results: Mean MDRD GFR at CA was 12.51 ± 3.51 ml/min. The trend was not significantly different 6 mo pre- and postangiography. Cumulative dialysis-free survival was 89.1% 6 mo postangiography. Twenty-three of 76 (30.3%) patients had flow-limiting coronary artery disease. Twenty-five of 76 (32.9%) patients underwent transplantation with 22 of 25 (88.0%) transplants being performed preemptively.
Conclusions: The data suggest CA screening does not accelerate the decline in renal function for patients with advanced CKD, facilitating a safe preemptive transplant program.
]]>Design, setting, participants, & measurements: We studied 858 incident patients in our incremental high-flux HD and online HDF program during an 18-yr period. We compared outcomes, including survival, in those who were treated predominantly with HDF (>50% sessions) and those with high-flux HD. Survival comparisons used a Cox model taking into account the time-varying proportion of time spent on HDF. All data were prospectively collected.
Results: A total of 152,043 sessions were delivered as HDF and 291,222 as high-flux HD. A total of 232 (27%) patients were treated predominantly with HDF and 626 (73%) with high-flux HD. Total Kt/V, serum albumin, erythropoietin resistance index, and BP were similar in both groups up to 5 yr after HD initiation. Intradialytic hypotension was less frequent in the predominant HDF group. Predominant HDF treatment was associated with a reduced risk for death after correction for confounding variables. In a second Cox model, proportion of time spent on HDF predicted survival, such that patients who were treated solely by HDF would have a hazard for death of 0.66 compared with those who solely used high-flux HD.
Conclusions: We found no benefits of HDF over high-flux HD with respect to anemia management, nutrition, mineral metabolism, and BP control. The mortality benefit associated with HDF requires confirmation in large randomized, controlled trials. These data may contribute to their design.
]]>Design, setting, participants & measurements: Samples were collected from 16 chronic hemodialysis patients using EDTA and gel-separator tubes. Plasma and serum were aliquoted; one aliquot was assayed with Elecsys and Liaison methods to determine the "baseline" values and another aliquot after 1, 3, 6, and 12 mo. The factors "method," "tubes," "subjects," and "time" were included in a mixed linear model to evaluate their effects on measured PTH values. The prediction interval methodology was used to assess where a future result could be obtained with a defined probability.
Results: With the Liaison method, the maximum storage times with either dry or EDTA tubes were estimated to be 9 and 2 mo, respectively. With the Elecsys method, samples could be stored at least 2 yr with acceptable level of degradation.
Conclusion: PTH stability at −80°C is not infinite. Maximum storage time and acceptance limits (30%) were defined, showing that with one method, samples should be stored for not more than 2 mo, whereas the other could be stored for up to 2 yr. With any PTH assay, the maximum storage time should be evaluated to ascertain that samples will keep their initial reactive profile after prolonged storage periods.
]]>Design, setting, participants, & measurements: Retrospective chart review of children on home continuous cycling PD between April 1, 2001 and June 30, 2007 was performed. Infection rates were examined based on exit site protocol used in two different periods: Mup alone, April 1, 2001 to November 17, 2004; and Mup and NaOCl (Mup+NaOCl), November 18, 2004 to June 30, 2007.
Results: Eighty-three patients (mean PD initiation age: 12.1 ± 5.8 yr) received home PD over 2009 patient months. Annualized rates (ARs) for peritonitis decreased from 1.2 in the Mup period to 0.26 in the Mup+NaOCl period (P < 0.0001). ARs for ESI/TI decreased from 1.36 in the Mup period to 0.33 in the Mup+NaOCl period (P < 0.0001). No infections with Mup-resistant organisms were observed when either Mup or Mup+NaOCl was used for prophylaxis. Gram-negative-organism associated peritonitis decreased from an AR of 0.31 in the Mup period to 0.07 in the Mup+NaOCl period (P < 0.001). Infection-related catheter removal rates decreased from 1 in 38.9 catheter-months in the Mup period to 1 in 94.2 in the Mup+NaOCl period (P = 0.01). Catheter survival rates were longer in the Mup+NaOCl period (Kaplan–Meier, P < 0.009).
Conclusions: The combination Mup+NaOCl in daily exit site care was very effective to reduce PD catheter-associated infections and prolong catheter survival in pediatric patients.
]]>Design, setting, participants, & measurements: Patients were randomly selected from among participants in the HUS-SYNSORB Pk trial. Plasma samples were collected on days 1, 4, 7, and 10 after enrollment and day 28 after discharge from the hospital. Levels of two complement pathway products, Bb and SC5b-9, were determined by ELISA.
Results: Seventeen children (6 boys and 11 girls; age, 5.4 ± 3.5 yr) were studied. Eight (47%) required dialysis support, and two had serious extrarenal events. On the day of enrollment, plasma levels of Bb and SC5b-9 were significantly increased in all patients compared with healthy controls (P < 0.01). The elevated concentrations normalized by day 28 after discharge. Circulating levels of complement pathway fragments did not correlate with severity of renal injury or occurrence of complications.
Conclusions: Patients with acute-onset D+HUS manifest activation of the AP of complement that is temporally related to the onset of disease and that resolves within 1 mo. Therapies to inhibit the AP of complement may be useful in attenuating the severity of renal injury and extrarenal complications.
]]>Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses’ Health Studies I and II (older and younger women).
Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01).
Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.
]]>Design, setting, participants, & measurements: This was an observational study of 15,368 adult participants in the National Health and Nutrition Examination Survey III; 5.9% had CKD (eGFR < 60 ml/min per 1.73 m2). Based on the frequency and intensity of leisure time physical activity obtained by a questionnaire, participants were divided into inactive, insufficiently active, and active groups. Time to mortality was examined in Cox models, taking into account the complex survey design.
Results: Inactivity was present in 13.5% of the non-CKD and 28.0% of the CKD groups (P < 0.001). In two separate multivariable Cox models, compared with the physically inactive group, hazard ratios (95% confidence intervals) of mortality for insufficiently active and active groups were 0.60 (0.45 to 0.81) and 0.59 (0.45 to 0.77) in the non-CKD subpopulation and 0.58 (0.42 to 0.79) and 0.44 (0.33 to 0.58) in the CKD subpopulation. These hazard ratios did not differ significantly between the CKD and non-CKD subpopulations (P > 0.3).
Conclusions: Physical inactivity is associated with increased mortality in CKD and non-CKD populations. As in the non-CKD population, increased physical activity might have a survival benefit in the CKD population.
]]>Design, settings, participants, & measurements: Individuals age 21 or less with kidney biopsy-proven lupus nephritis followed in the Glomerular Disease Collaborative Network were included. Cox regression models were used to evaluate predictors of relapse and end stage kidney disease (ESKD).
Results: Seventy-three subjects with a mean age of 15.6 ± 3.4 yr were included. Five-year kidney survival was 77%. Complete and partial remission rates within 1 yr of induction therapy were 25 and 64%, respectively. Relapse and ESKD rates were similar between complete and partial responders. Relapse occurred in 35% of responders (complete or partial) in 45 ± 32 mo. Disease relapse was a predictor of ESKD (HR = 10.12, P <ü0.0001). Treatment resistance was documented in African Americans more often than non-African Americans (eight versus 0; P = 0.03). ESKD HR associated with treatment resistance was 6.25, P <ü0.002.
Conclusions: Remission whether complete or partial is associated with improved kidney survival in children with lupus nephritis. Nephritis relapse is a strong predictor of progression to ESKD. Treatment resistance portends a high risk of ESKD and disproportionately affects African American children with lupus nephritis.
]]>Background and objectives: Academic nephrology faces increasing challenges in faculty hiring and development. However, it is unknown how these pressures have affected the number and demographics of academic nephrologists.
Design, setting, participants, & measurements: Using the Association of American Medical Colleges Faculty Roster database, changes were analyzed in MD nephrology, as well as other internal medicine subspecialty, faculty from 1998 to 2008.
Results: There were 1315 full-time MD nephrology faculty in 2008; this fell by 4.9% over the past decade. There were fewer junior, and more senior, faculty over this period. This was associated with 12.4% fewer tenured, 22.3% fewer tenure track, and an 11.5% increase in nontenure track, academic nephrologists. Academic nephrologists who are U.S. medical school graduates declined by 11.9%, while those who were international medical school graduates increased by 13.2%; nephrology has a greater percentage of international medical school graduates than any other internal medicine subspecialty. Female nephrology faculty increased by 14.3%, while male faculty fell by 9.5%. Asian nephrology faculty increased by 41.3%, while Caucasians declined by 15.2%. Similar changes in all the above parameters were seen for most other internal medicine subspecialties. The nephrology research programs at the top 20 research institutions, as compared with all other nephrology programs, had a greater decline in total MD, male, tenure track, and junior faculty.
Conclusions: These data suggest that the future of academic nephrology is at risk. The decline in nephrology faculty provides incentive for leaders in academic nephrology to improve recruiting and retention practices.
]]>Background and objectives: Hemodialysis (HD)-induced regional wall motion abnormalities (RWMAs) are common in HD patients and driven by ischemia. In nondialysis patients, repeated ischemia leads to chronic reduction in left ventricular (LV) function. HD-induced myocardial ischemia may initiate the same process. We examined the effect of HD-induced repetitive myocardial stunning on global and regional LV function.
Design, setting, participants & measurements: We analyzed data from 30 patients, previously identified as developing HD-induced myocardial ischemia. Serial echocardiographic assessments of global and regional LV performance were performed at baseline and repeated after 12 mo.
Results: Several patients developed segments with a fixed reduction in systolic function of >60% after 1 yr. In this patient group, there was a significant reduction in resting LV ejection fraction (EF) from 61.5 ± 10.1% to 52.9 ± 8.6% (P < 0.007). Peak LV EF in response to dialysis also decreased from 59.5 ± 10% versus 49.9 ± 6.5% (P < 0.003), with a consequent increase in HD-induced hypotension (P < 0.0001).
Conclusions: HD-induced myocardial stunning may progress over 12 mo to the development of regional fixed systolic dysfunction, consistent with underlying myocardial hibernation and fibrosis. This may be an important and potentially modifiable process in the development of heart failure in HD patients.
]]>Background and objectives: In medullary sponge kidney (MSK)—a common malformative renal condition in patients with calcium nephrolithiasis—hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither has the potential effect of potassium citrate administration (CA) on their urinary metabolic risk factors and on bone mineralization.
Design, setting, participants, & measurements: These issues were retrospectively analyzed in 75 patients with MSK and primary stone risk factor (PSRF; hypercalciuria, hypocitraturia, hyperuricosuria, and/or hyperoxaluria) on an outpatient basis; 65 received CA (2.9 ± 0.8 g/d), whereas 10 received only general "stone clinic" suggestions. The 24-h urinary excretion of calcium, phosphate, oxalate, uric acid, and citrate; morning urine pH; serum biochemistry; and bone mineral density were investigated at baseline and at the end of follow-up (78 ± 13 and 72 ± 15 mo in groups A and B, respectively).
Results: CA led to a significant rise in urinary pH and citrate and decreased urinary calcium and phosphate (all P < 0.001). Patients with MSK and PSRF had reduced bone density. Bone density improved significantly in the group that was treated with oral CA.
Conclusions: Bone disease is very frequent in patients with MSK and concomitant PSRF. Long-term CA improves bone density. The concurrent effects of treatment on PSRF suggest that the subtle acidosis plays a pivotal role in bone disease and hypercalciuria in patients with MSK.
]]>Background and objectives: This study investigated whether the slope of estimated GFR is different between nonproteinuric subjects with and without diabetes, and what clinical factors are associated with the GFR slope.
Design, setting, participants, & measurements: An observational cohort study was performed in 923 subjects, and the predictive value of baseline variables on the GFR slope was investigated.
Results: On the basis of the median 3-yr follow-up and 7 measurements of GFR, GFR slope (%/yr, median and interquartile range) was significantly larger in subjects with diabetes (-2.39 (-4.86 to 0.15), n = 729) than in those without diabetes (-1.02 (-4.28 to 1.37), n = 194), and this difference remained significant with or without presence of hypertension. After adjustments for confounding factors, predictors of GFR decline were found to be baseline high values of glycosylated hemoglobin A1C (HbA1C), GFR, systolic blood pressure, and low plasma total protein in subjects with diabetes, whereas only the latter two were significant in subjects without diabetes. In subjects with diabetes, the high GFR was accounted for by high HbA1C at baseline, and the predictors of GFR decline differed between those with and without hypertension, or with high and low baseline GFR. Any combination of the predictors showed increased risk for GFR decline.
Conclusions: GFR slope is substantially affected by multiple factors at various stages. The degree of chronic hyperglycemia is likely to play a crucial role in elevating GFR and accelerating the decline in patients with type 2 diabetes even from the normoalbuminuric stage.
]]>Background and objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for premature cardiovascular death in hemodialysis (HD) patients and one of the three forms of uremic cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a volume-independent technique to assess cardiac structure. We used CMR to assess the determinants of left ventricular mass (LVM) and LVH in HD patients.
Design, setting, participants, & measurements: A total of 246 HD patients (63.8% male; mean age 51.5 ± 12.1 yr) underwent CMR on a postdialysis day. LVM was measured from a stack of cine loops and indexed for body surface area (LVM index [LVMI]). Demographic, past biochemical, hematologic, and dialysis data were collected by patient record review. Results up to 180 d before CMR were collected. LVH was defined as LVMI >84.1 g/m2 (male) or >76.4 g/m2 (female).
Results: A total of 157 (63.8%) patients had LVH. LVH was more common in patients with higher predialysis systolic BP, predialysis pulse pressure, and calcium-phosphate product (Ca x PO4). Furthermore, LVH was significantly associated with higher end-diastolic and systolic volumes and lower ejection fraction. There were positive correlations with LVMI and end-diastolic and systolic volumes. There were weak positive correlations among LVMI, mean volume of ultrafiltration, and Ca x PO4. Using multivariate linear and logistic regression (entering one BP and cardiac variable), the independent predictors of LVMI and LVH were end-diastolic volume, predialysis systolic BP, and Ca x PO4.
Conclusions: The principal determinants of LVM and LVH in HD patients are end-diastolic LV volume, predialysis BP, and Ca x PO4.
]]>Background and objectives: Racial differences in mineral metabolism exist in the chronic kidney disease population, especially as it relates to intact parathyroid hormone (iPTH) levels. Few data exist on the relationship of these markers to bone biopsy findings in African-American (AA) hemodialysis patients across the spectrum of renal osteodystrophy (ROD).
Design, setting, participants, & measurements: In prevalent AA hemodialysis subjects, we prospectively evaluated subjects by performing transiliac bone biopsy and correlating biochemical and clinical data to bone histology.
Results: Study patients (n = 43) had an average age of 53.7 (±11.6) yr, with dialysis vintage of 40.4 (±24.5) mo, 30% with diabetes, and 51% male. Bone histology revealed adynamic bone disease (ABD) (16%), mild to moderate hyperparathyroidism (HPT) (72%), severe (12%) HPT, and no osteomalacia or mixed uremic osteodystrophy. At the time of biopsy, mean corrected calcium was 9.1, 8.9, and 9.4 mg/dl (P = 0.344); calcium-phosphorus (Ca x PO4) product was 42, 55, and 62 mg2/dl2 (P = 0.002); phosphorus was 4.6, 6.2, and 6.7 mg/dl (P = 0.005); and iPTH was 225, 566, and 975 pg/ml (P = 0.006), respectively. Median values for bone-specific alkaline phosphatase (BS-AP) were 16, 34, and 64 ng/ml (P < 0.0001) among the three groups.
Conclusions: These data demonstrate that across the spectrum of ROD, iPTH levels are higher than expected in AA hemodialysis subjects. iPTH, PTH peptides, and bone-specific alkaline phosphatase correlated directly with histomorphometric measurements of bone turnover and when subjects were grouped by histologic diagnosis. Only 9.5% of subjects were simultaneously within suggested Kidney Disease Outcomes Quality Initiative (K/DOQI) ranges for Ca x PO4, phosphorus, and iPTH, of which 75% demonstrated ABD on biopsy.
]]>Background and objectives: Hemodialysis needs an arteriovenous fistula (AVF) that may influence the structure and growth of nearby bone and affect bone mass measurement. The study analyzed the effect of AVF in the assessment of forearm bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA) and examined its influence on the final diagnosis of osteoporosis.
Design, setting, participants, & measurements: Forty patients (52 ± 18 yr) in hemodialysis program (12 ± 8 yr) with permeable AVF in forearm were included. Patients were divided in two groups (over and under 50 yr). BMD of both forearms (three areas), lumbar spine, and femur was measured by DXA. Forearm measurements in each arm were compared. Patients were diagnosed as normal only if all territories were considered nonpathologic and osteoporosis/osteopenia was determined by the lowest score found.
Results: Ten patients were excluded and 30 patients were analyzed. BMD in the forearm with AVF was significantly lower than that observed in the contralateral forearm in both groups of patients and in all forearm areas analyzed. When only lumbar spine and femur measurements were considered, 70% of patients were nonpathologic and 30% were osteoporotic. However, inclusion of AVF forearm classified 63% as osteoporotic and a further 27% as osteopenic, leaving only 10% as nonpathologic.
Conclusions: Forearm AVF affects BMD measurements by decreasing their values in patients with end-stage renal failure. This may produce an overdiagnosis of osteoporosis, which should be taken into account when evaluating patients of this type.
]]>Background and objectives: The kidney is important not only in the genesis of blood pressure elevation, but declining renal function is also important for predicting cardiovascular risk. The primacy of the kidney in causing essential hypertension was a topic of debate until the proof-of-principle experiment was performed, which demonstrated remission of essential hypertension in six African-American hypertensives with ESRD after they received successful kidney transplants from normotensive donors. The resolution of hypertension and hypokalemia in a patient with Liddle’s syndrome and ESRD after subsequent successful renal transplantation also demonstrated the primacy of the kidney in a monogenic form of hypertension related to sodium epithelial channel dysfunction.
Design, setting, participants, & measurements: A review of the available evidence linking cardiovascular disease with chronic kidney disease.
Results: The cause for the inverse continuous relationship between kidney function and cardiovascular events in patients with native kidney disease and kidney transplant recipients is unknown but may be related to traditional and nontraditional cardiovascular risk factors. This is an important clinical concern and requires close attention to cardiovascular risk reduction measures.
Conclusions: Increased cardiovascular disease in patients with chronic kidney disease is an important clinical concern. Improved biomeasures of cardiovascular risk and response to therapy are needed.
]]>Background and objectives: Creatinine-based estimates of GFR suggest an evolving epidemic of chronic kidney disease (CKD) in U.S. adults that is inadequately explained by conventional, modifiable risk factors. Cystatin C has recently emerged as a promising measure of GFR. To enable further insights into the evolution of CKD in the U.S. population, this study aimed to examine cystatin C levels in U.S. adults.
Design, setting, participants, and measurements: Stored serum samples, measured in 2006, were used to compare cystatin C levels among adult participants in the National Health and Nutrition Examination Survey (NHANES) in two time periods, 1988–1994 (n = 6877) and 1999–2002 (n = 4563).
Results: Mean cystatin C levels (0.9 versus 0.9 mg/L, P = 0.65) and urinary albumin-creatinine ratios were similar (5.8 versus 5.9 mg/g, P = 0.19) in the 2 study eras. In contrast, standardized serum creatinine (0.8 versus 0.9 mg/dl, P < 0.0001) was higher and estimated GFR (93.2 versus 87.6 ml/min/1.73 m2, P < 0.001) was lower in 1999–2002. Similar discrepancies in population trends (when cystatin C and creatinine-based methods were used to define GFR) were present when categories of kidney function were considered, and when adjustment was made for demography and comorbid illness.
Conclusions: The disparity between temporal trends when kidney function is assessed with different measurements suggests that estimating trends in disease burden remains an open question.
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