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Chronic kidney disease (CKD) is a significant public health problem: every year the number of Americans living with CKD and requiring renal replacement therapy increases. In addition, individuals with CKD have substantially increased morbidity and mortality compared to the general population. The Longitudinal Chronic Kidney Dialysis (LCKD) Study is a multicenter, prospective, observational study of patients with moderate to severe CKD that was designed to better describe the course of the disease and the determinants of patient outcomes. Patients with moderate to severe CKD (glomerular filtration rate [GFR]60 ml/min/m2) from four academic nephrology clinics were enrolled between 2000 and 2002. Special cardiac and vascular testing has recently commenced as phase II of this study. Areas that have been or are currently being studied include anemia management, health-related quality of life (HRQOL), medication use, and markers of cardiovascular disease. This article describes the LCKD Study in the context of current knowledge of CKD.

Dialysis access monitoring may help decrease thrombosis-related morbidity. We investigated the effect of time elapsed since an access flow measurement on test accuracy of a novel flow monitoring method called variable flow (VF) Doppler. A retrospective review was conducted in 36 patients with prosthetic grafts for vascular access using access thrombosis as the clinical endpoint. Receiver operator characteristic (ROC) curves and test sensitivity and specificity were determined for various follow-up time intervals. ROC analysis showed increasing test discrimination for shorter time intervals. Sensitivity and specificity for a commonly used surveillance threshold (600 ml/min) showed specificity that was little changed (88-93%) from follow-up time intervals of 15 days to 6 months. However, sensitivity was low (21%) at 6 months, increased to 50% at 2 months, 67% at 1 month, and 100% at 15 days (a single event). Low access blood flow using VF Doppler predicts near-term thrombosis. These data further imply that the discriminative value of access flow monitoring appears to be highly dependent on time from the flow measurement, improving with shorter time intervals from the measurement.

VA serves as a lifeline for HD patients. VA-related expenditures are the largest component of dialysis-related costs. Wide variations in VA practices and outcomes around the world have emerged from analysis of the DOPPS data. Both patient and practice pattern-related factors determine type of VA placed as well as VA outcomes. Type of VA is associated with patient survival after adjustment for case mix. A multidisciplinary approach is crucial for success of any VA program with emphasis on pre-ESRD planning and implementation. AVF should serve as the gold standard. Use of catheters should be minimal, but this will likely remain a challenge for some time. Observational data suggest that earlier cannulation of AVF may not be as deleterious as previously thought. Clinical trials are sorely needed in many aspects of VA management to improve both VA and patient outcomes.

While there have been significant inroads in the prevention and treatment of diabetic nephropathy over the last 20 years, it only takes one afternoon in a busy nephrology clinic to recognize that diabetic nephropathy remains the major clinical challenge in nephrology today. The 2011 US Renal Data

Background: Several drugs have been proposed to improve vascular access patency based on favorable anticoagulant, antiplatelet, or vascular-remodeling properties. However, there is little evidence to guide drug strategies. Methods: The association between vascular access patency and the use of specific drugs was studied in a large sample of US hemodialysis patients enrolled in the Dialysis Outcomes and Practice Patterns Study, an international, prospective, observational study. In general, it was assumed that the drugs were prescribed for indications unrelated to vascular access preservation. Primary (unassisted survival) and secondary vascular access patency (assisted survival) were modeled using Cox regression (time to failure) adjusted for age, sex, race, body mass index, incidence to end-stage renal disease, diabetes mellitus, hypertension, valvular disease, chronic obstructive pulmonary disease, aortic aneurysm, deep-vein thrombosis, number of previous permanent accesses, and facility-clustering effects. Fistulae (n = 900) and grafts (n = 1,944) were evaluated separately. Technical failures within the first 30 days of surgical placement were excluded from the analysis. Results: Treatment with calcium channel blockers was associated with improved primary graft patency (relative risk [RR] for failure, 0.86; P = 0.034). Aspirin therapy was associated with better secondary graft patency (RR, 0.70; P P = 0.010). Patients administered warfarin showed worse primary graft patency (RR, 1.33; P = 0.037). Conclusion: These findings should help guide clinical trial priorities toward vascular access preservation using one or more of the agents that show significant risk reduction for access failure in this study. Am J Kidney Dis 40:1255-1263. © 2002 by the National Kidney Foundation, Inc.

Background: Left ventricular hypertrophy (LVH) is common among patients with end-stage renal disease (ESRD), but few population-based studies exist. Here, we describe clinical correlations and mortality impact of LVH in new patients with ESRD from the Dialysis Morbidity and Mortality Study Wave 2. Methods: Echocardiographic data denoting the presence or absence of LVH were available for 64% (n = 2,584) of the entire cohort. Multivariate logistic regression identified significant correlates of LVH, and Cox proportional hazards regression estimated the mortality risk (risk ratio [RR]) for LVH at 6, 12, and 24 months. Results: The prevalence of LVH was 16.4%. Multivariate analysis identified age (adjusted odds ratio [OR], 1.15 per 10 years older), hypertension (OR, 1.39), diabetes (OR, 1.47), tobacco use (OR, 1.42), serum calcium level (OR, 1.17 per 1 mg/dL [0.25 mmol/L] higher), parathyroid hormone level greater than versus less than 157 pg/mL (157 ng/L; OR, 1.53), serum albumin level (OR, 1.38 per 1 g/dL [10 g/L] lower), and presence of pericarditis (OR, 2.55) as significant disease correlates. The impact of LVH on subsequent mortality was greatest in the first 6 months of follow-up (RR, 1.61; confidence interval [CI], 1.17 to 2.22) and became less pronounced thereafter (RR, 1.36; CI, 1.07 to 1.89; RR, 1.29; CI, 1.07 to 1.56 at the end of 1 and 2 years, respectively). Conclusion: This study identifies known coronary risk factors and markers of uremia as independent correlates of LVH presence in new patients with ESRD. It also highlights the adverse impact of pre-ESRD LVH on short-term patient survival. Given the clinical consequences of LVH on morbidity and mortality, greater efforts are required to reduce known risk factors for LVH in the pre-ESRD period. Am J Kidney Dis 40:1102-1110. © 2002 by the National Kidney Foundation, Inc.

Background Diet can markedly affect acid-base status and it significantly influences chronic kidney disease (CKD) and its progression. The relationship of dietary acid load (DAL) and CKD has not been assessed on a population level. We examined the association of estimated net acid excretion (NAEes) with CKD; and socio-demographic and clinical correlates of NAEes. Methods Among 12,293 U.S. adult participants aged >20 years in the National Health and Nutrition Examination Survey 1999–2004, we assessed dietary acid by estimating NAEes from nutrient intake and body surface area; kidney damage by albuminuria; and kidney dysfunction by eGFR < 60 ml/min/1.73m2 using the MDRD equation. We tested the association of NAEes with participant characteristics using median regression; while for albuminuria, eGFR, and stages of CKD we used logistic regression. Results Median regression results (β per quintile) indicated that adults aged 40–60 years (β [95% CI] = 3.1 [0.3–5.8]), poverty (β [95% CI] = 7.1 [4.01–10.22]), black race (β [95% CI] = 13.8 [10.8–16.8]), and male sex (β [95% CI] = 3.0 [0.7- 5.2]) were significantly associated with an increasing level of NAEes. Higher levels of NAEes compared with lower levels were associated with greater odds of albuminuria (OR [95% CI] = 1.57 [1.20–2.05]). We observed a trend toward greater NAEes being associated with higher risk of low eGFR, which persisted after adjustment for confounders. Conclusion Higher NAEes is associated with albuminuria and low eGFR, and socio-demographic risk factors for CKD are associated with higher levels of NAEes. DAL may be an important target for future interventions in populations at high risk for CKD.

A severely burned patient receiving neutral phosphate supplement developed renal tubular alkalosis. This phenomenon is compared with the results of experimental observations on animals, reported in the literature. The physiologic mechanism, including the possible role of parathyroid hormone, is illustrated.

Age as a factor in the decision to refer patients with chronic kidney disease for vascular access creation

We (Perit Dial Int 17:426 and 497, 1997) and the Dialysis Outcomes Quality Initiative guidelines (Am J Kidney Dis 30:S69, 1997) have reported evidence that protein intake often is0.8 g/kg standard weight when renal weekly urea clearance (L) normalized to total body water (V, L) is less than 2.0, and that initiation of dialysis should be considered if nutritional status is decreasing. We have prospectively followed renal urea (C(urea)) and creatinine clearances (C(cr)) in 20 patients with chronic renal failure. Nine patients received dietary counseling, but we have previously shown this has minimal effects on protein intakes (Perit Dial Int 17:497, 1997). In 16 patients (group 1), glomerular filtration rate (GFR) estimated as (C(urea) + C(cr))/2 decreased from 14.6 +/- 1.5 (mean +/- SEM) to 9.8 +/- 0.9 (ml/min/1.73 m2 BSA) over a mean interval of 10.3 +/- 1.6 months; in the other 4 patients (group 2), mean GFR did not decrease and was initially 17.6 +/- 3.8 and 21.7 +/- 2.2 after 8.5 +/- 2.3 months. In group 1, Kt/V went from 2.5 +/- 0.3 to 1.7 +/- 0.2; in group 2, Kt/V went from 3.1 +/- 1.0 to 3.7 +/- 0.6. In group 1, protein intake as assessed from the normalized equivalent of protein nitrogen appearance calculated from urea nitrogen and protein losses in urine (nPNA; g/kg standard weight) went from 1.0 +/- 0.1 to 0.8 +/- 0.1. In group 2, mean nPNAs were 1.1 +/- 0.3 and 1.1 +/- 0.1. In all measurements with Kt/V less than 2.0 (n = 18), 10 (56%) were with nPNA less than 0.8. In all measurements of Kt/Vor = 2.0 (n = 22), only 3 (13.6%) were with an nPNA of less than 0.8. These percentage values were different (p0.0001) by chi-squared analysis. Changes in nPNA correlated directly (but insignificantly, probably because of a small n) with C(cr), GFR, and Kt/V. These prospective results provide additional evidence that protein intakes decrease to dangerously low levels (without intense dietary monitoring) in most patients when renal weekly Kt/V decreases to below 2.0, which is similar to findings in patients on continuous ambulatory peritoneal dialysis.

Peritoneal dialysis (PD) is a safe, effective, low-cost intracorporeal renal replacement modality with some inherent advantages. The peritoneal membrane is a biocompatible, internally located dialyzer which limits ingress of bacteria and their products, removes uremic toxins, allows continuous, gentle 24-hour dialysis and ultrafiltration, while avoiding the use of anticoagulants [l, 2].

We are grateful to Dr Okamoto et al.1 for providing insightful comments in response to our published paper dealing with the issues of treatment time (TT) and ultrafiltration rate (UFR) in the Dialysis Outcomes and Practice Patterns Study.2 We wish to respond to the three main points they make. (I) They speculate that the reason for the relatively strong correlation observed between TT and Kt/V in Japan is because TT in Japan is decided based on total ultrafiltration volume, whereas in Europe and the US, TT is more dependent on target Kt/V. They also make the point that it is perhaps easier to achieve target Kt/V in Japan owing to the relatively smaller body size of the Japanese patients (we agree with this statement). We have previously observed in the Dialysis Outcomes and Practice Patterns Study that interdialytic weight gains are, on average, relatively higher in Japan.3 It may well be that TT in Japan is usually at or above 4 h because they target the ultrafiltration volume over a longer time owing to the belief that longer TT is useful in the delivery of hemodialysis, a practice pattern that reflects achievement of dialysis adequacy by prolonging time (as we discuss in the paper) rather than other measures such as higher blood flow rate or utilization of larger dialyzers which are more likely to be used in the US. (II) It is quite possible that low UFR is generally applied when patient's blood pressure is low predialysis, or for the prevention of intradialytic hypotension. Even if there is such confounding as Dr Okinamoto et al. suggest, the results are independent of the multiple co-morbidities that were adjusted for in our analyses, and suggest that low UFR may actually be protective for all-cause mortality. We agree that low UFR may be more weakly associated with reduced cardiovascular mortality because of the fact that it is confounded by low blood pressure, which itself is a predictor of higher mortality in dialysis patients. However, this hypothesis would need to be tested formally. (III) We recognized that both UFR (ml/min/kg) and Kt/V have 'T' in them. However, the Cox proportional hazards models have both variables simultaneously and TT. Despite potential collinearity, the variables are independently associated with outcomes. Furthermore, we reported an interaction between Kt/V and T, such that for any Kt/V a longer time was independently protective. This interaction directly addresses the 'time-limited Kt/V' issue, which is raised in the letter. Overall, the points made by Drs Okamoto, Kobayashi and Noiri do not argue against the validity of our reported significant correlations of TT and UFR with mortality risk, but suggest that our report may offer an underestimate of the true magnitude of potential benefits from longer TT and slower UFR.

Background. Kidney donors are not adversely affected by compensatory hyperfiltration of the remaining kidney in the early years after nephrectomy, but long-term longitudinal studies are lacking. Methods. The renal function and blood pressure of 75 donors was evaluated in 1984, 1.4-20.7 years after surgery. Forty-seven of the original cohort (23 male, age 38-80 years) underwent repeat study a decade later (12-31 years post-nephrectomy), using identical laboratory techniques. Results. Glomerular filtration rates (GFR) as measured by 51 Cr EDTA clearance was relatively unchanged a decade later with 41 of 47 subjects (87%) having EDTA clearance within the normal laboratory reference range at review. The change in GFR in the remaining six subjects was statistically not significant. No correlation between GFR and time after nephrectomy was detected. Albumin excretion rate (AER), on timed overnight urine collections, was increased (> 20 μg/min) in 16 subjects (34%), although 14 of these individuals were also hypertensive. The prevalence of hypertension was significantly increased compared with age/sex matched data from epidemiological studies of the general population (both in the UK and the US), especially in those over the age of 55 years. Conclusion. This study demonstrates that the function of the solitary kidney is not adversely affected by prolonged compensatory hyperfiltration, although there appears to be an increased prevalence of microal-buminuria and hypertension. Regular follow-up of kidney donors is recommended in order to manage their complications effectively and to detect hypertension and or renal impairment early in those who may develop it.

Chronic Kidney Disease Surveillance for the United States: A Centers for Disease Control and Prevention Initiative Elizabeth Hedgeman, Laura Plantinga, Nilka Rios Burrows, Jerry Yee, Neil Powe, Desmond Williams and Rajiv Saran for the CDC CKD Surveillance System. University of Michigan, Ann Arbor, MI; University of California, San Francisco, CA; Centers for Disease Control and Prevention, Baltimore, MD; Henry Ford Health System, Detroit, MI. Chronic kidney disease (CKD) affects 10-15% of the population within the US, yet no comprehensive system has thus far existed to track the disease and its outcomes. In 2006, the Centers for Disease Control and Prevention (CDC), as a major part of its CKD Initiative, funded two teams to jointly develop and implement a CKD surveillance system. A Steering Committee and Advisory Group of external stakeholders provided input toward selection of priority measures and key data sources. Data from national and regional data sources have been analyzed and comprehensive written reports submitted to the CDC since 2008. All findings of the CDC CKD Surveillance System will be available at www.cdc.gov/ckd by early 2011. The website covers priority measures under six major topic areas (burden of disease, awareness, risk factors, health consequences, processes and quality of care and healthcare system capacity for CKD) from a variety a data sources selected to represent the population. Figures and tables of specific measures will be updated regularly including relevant stratifications and time trends. The system will evolve to reflect feedback, scientific advances and changing patterns of disease. We believe that the CDC CKD Surveillance System will heighten awareness and provide timely information to regulatory agencies, research and clinical communities, and the general public, thereby providing a solid basis toward stemming the national epidemic of CKD.

Albuminuria is associated with an increased risk of death independent of level of renal function. Whether this association is similar for adults of all ages is not known.We examined the association between the albumin to creatinine ratio (ACR) and all-cause mortality after stratification by estimated glomerular filtration rate (eGFR) and age group in 94 934 veterans with diabetes mellitus. Cohort members had at least 1 ACR recorded in the Veterans Affairs Health Care System between October 1, 2002, and September 30, 2003, and were followed up for death through October 15, 2009.From the youngest to the oldest age group, the prevalence of an eGFR less than 60 mL/min/1.73 m(2) ranged from 11% to 41%; microalbuminuria (ACR 30-299 mg/g) ranged from 19% to 28%; and macroalbuminuria (ACRor =300 mg/g) ranged from 3.2% to 3.7%. Of patients with an eGFR less than 60 mL/min/1.73 m(2), 72% of those younger than 65 years, 74% of those 65 to 74 years old, and 59% of those 75 years and older had an eGFR of 45 to 59 mL/min/1.73 m(2). In all age groups, less than 35% of these patients had albuminuria (ie, ACRor =30 mg/g). In patients 75 years and older, the ACR was independently associated with an increased risk of death at all levels of eGFR after adjusting for potential confounders. In younger age groups, this association was present at higher levels of eGFR but seemed to be attenuated at lower levels [corrected].The ACR is independently associated with mortality at all levels of eGFR in older adults with diabetes and may be particularly helpful for risk stratification in the large group with moderate reductions in eGFR.

Background The impact of recent guidelines for early detection and prevention of chronic kidney disease (CKD) on patient awareness of disease and factors that might be associated with awareness have not been well described. Methods Awareness rates were assessed in 2992 adults (age, ≥20 years) with CKD stages 1 to 4 from a nationally representative, cross-sectional survey (National Health and Nutrition Examination Survey 1999-2004). Awareness of CKD was defined by an answer of yes to “Have you ever been told you have weak or failing kidneys?” Potential predictors of awareness included demographics, access to care, and clinical and lifestyle factors, which were assessed by standardized interviewer-administered questionnaires and physical examinations. We examined independent associations of patient characteristics with awareness in those with CKD stage 3 (n = 1314) over 6 years using multivariable logistic regression. Results Awareness improved over time in those with CKD stage 3 only (4.7% [95% confidence interval {CI}, 2.6%-8.5%], 8.9% [95% CI, 7.1%-11.2%], and 9.2% [95% CI, 6.1%-13.8%] for 1999-2000, 2001-2002, and 2003-2004, respectively; P = .04, adjusted for age, sex, and race). Having proteinuria (odds ratio, 3.04 [95% CI, 1.62-5.70]), diabetes (OR, 2.19 [95% CI, 1.03-4.64]), and hypertension (OR, 2.92 [95% CI, 1.57-5.42]) and being male (OR, 2.06 [95% CI, 1.15-3.69]) were all statistically significantly associated with greater awareness among persons with CKD stage 3 after adjustment. Chronic kidney disease awareness increased almost 2-fold for those with CKD stage 3 over recent years but remains low. Persons with risk factors for CKD (proteinuria, diabetes, hypertension, and male sex) were more likely to be aware of their stage 3 disease. Conclusion Renewed and innovative efforts should be made to increase CKD awareness among patients and health care providers.

The protein equivalent of nitrogen appearance normalized to standard weight was determined from urea nitrogen appearance (nPNA U) and from total Kjeldahl nitrogen appearance (nPNA K) in dialysate and/or urine in 45 predialysis patients (pre D) and in 95 patients on continuous ambulatory peritoneal dialysis (CAPD). Correlations with weekly Kt/Vurea and creatinine clearance (Ccr, L/wk/1.73 m2) were determined; renal contributions of CCr in both populations were calculated both as total CCr (A) and as CCr by GFR (CCr [B], mean of renal CCr and Curea). Correlations with weekly Kt/Vurea were significant in individual (pre D:nPNA U 0.57, p < 0.01, and nPNA K 0.37, p < 0.01; CAPD:nPNA U 0.50, p < 0.01, and nPNA K 0.43, p < 0.01) and pooled populations (nPNA U 0.54, p < 0.01 and nPNA K 0.37, p < 0.01). Correlations with neither Ccr (A) nor Ccr (B) were significant. The data also allowed comment on mathematical coupling. Ccr vs nPNA K correlations share even more mathematical couplers than does the nPNA K vs Kt/Vurea correlation, yet the correlation of nPNA K with Ccr is quite low. The authors conclude that urea is a better surrogate marker of small molecular weight toxins that inhibit protein intake in uremia, and correlations of nPNA with Kt/Vurea represent more than simple mathematical coupling.

Chronic peritoneal dialysis in iron-deficient rats with solutions containing iron dextran. Background We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane. Methods Seventy-two male Sprague-Dawley rats weighing 85 to 110 g were divided into two groups and seven subgroups. Group I consisted of rats on iron-deficient chow, and group II consisted of rats on normal chow. Both groups contained dialysis control subgroups ( N = 12: IA, IID), dialyzed with Dianeal® solution, and tissue control subgroups ( N = 6: IE, IIN), in which rats were not dialyzed and catheters were not implanted. Study group I contained the following study subgroups ( N = 12): (B) rats dialyzed with Dianeal® solution containing 2 mg/L of iron dextran and (C) rats dialyzed with Dianeal® solution containing 1 mg/L of iron dextran. Group IID was dialyzed with Dianeal® solution containing 2 mg/dL of iron dextran. Study duration was 12 weeks with peritoneal equilibration tests (PETs) performed at baseline, 6 weeks, and 12 weeks. Prior to baseline, rats were placed on iron-deficient chow or normal chow for three weeks. Dialysis was performed with three 25 mL volume exchanges per day. Hematocrit (Hct), serum iron (Fe), and total iron binding capacity (TIBC) were determined for each study interval. After the final PET, the animals were sacrificed, and the peritoneal membrane was evaluated by gross inspection and light microscopy. Results Rats on an iron-deficient diet developed severe iron-deficiency anemia after three weeks of the diet (Hct 27; Fe 21 to 23; TIBC 799 to 806). After 12 weeks, the rats remained anemic in groups A (Hct 34 ± 0.9; Fe 16 ± 2; TIBC 998 ± 27) and IE (Hct 38 ± 2.7), whereas the rats corrected anemia in group B (Hct 45.8 ± 1.8; Fe 115 ± 15; TIBC 546 ± 77). The results were not significantly different from those of group IID (Hct 47.1 ± 1.6; Fe 94 ± 19; TIBC 516 ± 46). In group C, Hct (44.8 ± 2.1) and Fe (94 ± 19) did not differ significantly from group IID, but TIBC (734 ± 76) remained significantly higher than that in the group IID. Peritoneal iron deposits were not detected. The morphometric analysis of the submesothelial space did not reveal any difference in thickness between dialysis groups. PETs were not significantly different among groups. Conclusions Intraperitoneal iron dextran supplementation in concentrations of 2 mg/L of dialysis solution is nontoxic to the peritoneum and effective in correcting iron deficiency in rats maintained on an iron-deficient diet. Iron dextran in concentration of 1 mg/L of dialysis solution may be sufficient for correcting a lesser degree of iron deficiency.

To the Editor: Liu and Foley (LF)1 question the methods in our analysis of day-of-week effects.2 Arguing that mortality on the day following the weekend (day 1) is of primary interest, they present a hypothetical example in which the death rates for days 1–7 are 10, 1, 1, 1, 1, 1, and 1, respectively, and note that the comparison of day 1 with the average of days 2–7 should yield a relative risk (RR) of 10. Our method would compare the log rate for day 1 with the average of the log rates for days 1–7 to obtain an RR=7.2 (not 4.4 as LF have stated), which, they claim, understates the true RR. In fact, the log RR in our analysis is 6/7 times theirs, and hence these two approaches yield the same test statistic and P-value.