Overweight, obesity and intentional weight loss in chronic kidney disease: NHANES 1999-2006.

OBJECTIVE: Obesity and chronic kidney disease (CKD) have emerged as major public health problems. We aimed to examine: (a) lifestyle and behavioral factors, (b) factors related to pursuing weight loss and (c) weight loss modalities pursued by CKD and non-CKD individuals who are overweight and obese. METHODS: Cross-sectional analysis of 10,971 overweight and obese adult participants in the National Health and Nutrition Examination Surveys conducted between 1999 and 2006. We examined the differences in lifestyle and behavioral factors between CKD and non-CKD participants and factors associated with pursuing weight loss using survey regression models. RESULTS: The total daily energy intake of the CKD population was lower than the non-CKD group (1987 kcal per day versus 2063 kcal per day, P=0.02) even after adjusting for relevant covariates. However, the percentage of energy derived from protein was similar between the groups. Sixty six percent of the CKD population did not meet the minimum recommended leisure time physical activity goals compared with 57% among non-CKD (P<0.001). Fifty percent of CKD participants pursued weight loss (vs fifty-five percent of non-CKD individuals, P=0.01), but the presence of CKD was not independently associated with the pursuit of weight loss in the multivariate model. Among participants pursuing weight loss, modalities including dietary interventions utilized by CKD and non-CKD participants were similar. Eight percent of CKD participants used medications to promote weight loss. CONCLUSIONS: Among the overweight and obese population, lifestyle and behavioral factors related to obesity and weight loss are similar between CKD and non-CKD participants. Insufficient data exist on the beneficial effects of intentional weight loss in CKD and these data show that a significant proportion of the CKD population use diets that may have high-protein content and medications to promote weight loss that may be harmful. Future clinical trials evaluating the efficacy and optimal modalities to treat obesity in the CKD population are warranted.

BioJava: an open-source framework for bioinformatics.

SUMMARY: BioJava is a mature open-source project that provides a framework for processing of biological data. BioJava contains powerful analysis and statistical routines, tools for parsing common file formats and packages for manipulating sequences and 3D structures. It enables rapid bioinformatics application development in the Java programming language. AVAILABILITY: BioJava is an open-source project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from the BioJava website (http://www.biojava.org). BioJava requires Java 1.5 or higher. All queries should be directed to the BioJava mailing lists. Details are available at http://biojava.org/wiki/BioJava:MailingLists.

Renal outcome 25 years after donor nephrectomy.

PURPOSE: The extended outcome after kidney donation has been a particular concern ever since the recognition of hyperfiltration injury. Few published reports have examined donor renal outcome after 20 years or greater. Kidney transplantation has been performed at the Cleveland Clinic Foundation since 1963, at which there is extensive experience with live donor transplantation. We assess the impact of donor nephrectomy on renal function, urinary protein excretion and development of hypertension postoperatively to examine whether renal deterioration occurs with followup after 20 years or greater. MATERIALS AND METHODS: From 1963 to 1975, 180 live donor nephrectomies were performed at the Cleveland Clinic. We attempted to contact all patients to request participation in our study. Those 70 patients who agreed to participate in the study were mailed a package containing a 24-hour urine container (for assessment of creatinine, and total protein and albumin), a vial for blood collection (for assessment of serum creatinine) and a medical questionnaire. All specimens were returned to and processed by the Cleveland Clinic medical laboratories. Blood pressure was taken and recorded by a local physician. A 24-hour creatinine clearance and the Cockcroft-Gault formula were used to estimate renal function, and values were compared with an age adjusted glomerular filtration rate for a solitary kidney. RESULTS: Mean patient followup was 25 years. The 24-hour urinary creatinine clearance decreased to 72% of the value before donation. For the entire study cohort serum creatinine and systolic blood pressure after donation were significantly increased compared with values before, although still in the normal range. The overall incidence of hypertension was comparable to that expected in the age matched general population. There was no gender or age difference (younger or older than 50 years) for 24-hour urinary creatinine clearance, or change in serum creatinine before or after donation. Urinary protein and albumin excretion after donation was significantly higher in males compared with females. There were 13 (19%) subjects who had a 24-hour urinary protein excretion that was greater than 0.15 gm./24 hours, 5 (7%) of whom had greater than 0.8. No gender difference was noted in blood pressure, and there were no significant changes in diastolic pressure based on gender or age. CONCLUSIONS: Overall, renal function is well preserved with a mean followup of 25 years after donor nephrectomy. Males had significantly higher protein and albumin excretion than females but no other clinically significant differences in renal function, blood pressure or proteinuria were noted between them or at age of donation. Proteinuria increases with marginal significance but appears to be of no clinical consequence in most patients. Patients with mild or borderline proteinuria before donation may represent a subgroup at particular risk for the development of significant proteinuria 20 years or greater after donation. The overall incidence of proteinuria in our study is in the range of previously reported values after donor nephrectomy.

Setting the stage.

Intradialytic hypotension (IDH) occurs during 25% to 50% of end-stage renal disease (ESRD) hemodialysis (HD) treatments. The development of IDH signals both technology- and patient-dependent limitations expressed across a broad range of symptoms, from nausea and muscle cramps to ischemic injury. While traditional thinking has emphasized the link between hypertension and cardio-cerebrovascular injury, more recent studies of ESRD patients have stimulated significant interest in hypotension and poor outcomes. Theoretically, hypotension can contribute to the increased relative risk of death in ESRD by several mechanisms, which include acute coronary syndrome, autoregulation dysfunction, ischemia, and arrhythmogenicity. Endothelial abnormalities (increased procoagulation, thrombogenecity risk, and alterations in coronary flow reserve) and altered vascular distribution within the myocardium provide an environment for vascular injury. The current symposia will examine the pathophysiology of IDH, the specific HD prescription modifications to prevent IDH, and newer pharmacologic interventions to treat IDH and will highlight the approach to several clinical cases based on the information presented. It is becoming increasingly important to identify patients at "high risk" for IDH, to customize the HD prescription to the individual patient, to use drug therapy to prevent IDH events, and to track the prevalence of chronic hypotension and the incidence of IDH complications in the dialysis unit.

Clinical case-based approach to understanding intradialytic hypotension.

The approach to end-stage renal disease (ESRD) patients who develop intradialytic hypotension (IDH) encompasses an understanding of the pathophysiology, appropriate dialysis prescription modification, application of newer pharmacologic therapies, and development of strategies for prevention. Patients should have a "minimal data set" as part of their predialysis assessment. This information is critical to prescription modifications that may help decrease the risk for IDH. Individuals at "high risk" for IDH should be kept to a "safe zone" for dialysis ultrafiltration (

Isolevuglandin-protein adducts in humans: products of free radical-induced lipid oxidation through the isoprostane pathway.

A family of extremely reactive electrophiles, isolevuglandins (isoLGs), is generated in vivo by free radical-induced lipid oxidation and rearrangement of endoperoxide intermediates of the isoprostane pathway. Protein adducts of two different oxidized lipids, isoLGE(2) and iso[4]LGE(2), and the corresponding autoantibodies are present in human blood. Western blot analysis of a polyacrylamide gel electrophoresis gel detects several immunoreactive plasma proteins. Only a minor fraction of the isoLG-protein modifications is associated with low density lipoprotein since mean levels were decreased only 20-22% by immunoprecipitation of apolipoprotein B (apoB). Mean levels of both isoLGE(2) and iso[4]LGE(2)-protein adducts in plasma from patients with atherosclerosis (AS) (n=16) or end-stage renal disease (RD) (n=8) are about twice those in healthy individuals (n=25). These elevated levels are not related to variations in age, total cholesterol or apoB. A linear correlation (r=0.79) between plasma isoLGE(2) and iso[4]LGE(2)-protein adduct levels in all 49 individuals is consistent with a common free radical-induced mechanism for the production of both oxidized lipids in vivo. The correlation is even stronger (r=0.86) for patients with AS or RD. That isoLG-protein adduct levels are more strongly correlated with disease than are total cholesterol or apoB suggests an independent defect that results in an abnormally high level of oxidative injury associated with AS and RD.

Prevalence and determinants of hyperhomocysteinemia in hemodialysis and peritoneal dialysis.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for atherosclerotic complications in patients with end-stage renal disease, although the mechanisms remain unclear. The major determinants of plasma homocysteine concentration are usually folate, vitamin B12, pyridoxal 5'-phosphate (vitamin B6), and glomerular filtration rate. METHODS: We measured factors, including plasma folate, vitamin B12, vitamin B6, creatinine, as well as the dose and duration of dialysis, that might affect plasma homocysteine concentrations in 130 patients on hemodialysis (HD) and compared these observations with those in 46 patients on peritoneal dialysis (PD). Independent determinants of total homocysteine were identified using a multiple logistical regression analysis. RESULTS: Total homocysteine values averaged 29.8 mumol/liter in HD patients, significantly higher than the mean value of 19.9 mumol/liter observed in patients on PD (P < 0.001). The prevalence of hyperhomocysteinemia was 90.8% among HD patients, significantly higher than the prevalence of 67.4% among PD patients. Folate values in HD patients averaged 45.5 nmol/liter and were significantly lower than in PD patients (104.2 nmol/liter, P < 0.001). For patients on HD, the only determinant of total homocysteine concentration was plasma folate (r = -0.31, P < 0.001). In contrast, for PD patients, total homocysteine did not correlate with plasma folate, vitamin B12, or vitamin B6. CONCLUSIONS: Hyperhomocysteinemia is more prevalent and intense in HD patients compared with those on PD. The homocysteine response may become refractory to excess folate supplementation in PD patients.

Measurement of oxidation in plasma Lp(a) in CAPD patients using a novel ELISA.

BACKGROUND: LGE2 is produced by the cyclooxygenase- or free radical-mediated modification of arachidonate and is formed during the oxidation of low density lipoprotein (LDL) with subsequent adduction to lysine residues in apo B. We have developed a sensitive enzyme-linked sandwich immunosorbent assay (ELISA) for detection and measurement of LGE2-protein adducts as an estimate of oxidation of plasma LDL and Lp(a). METHODS: The assay employs rabbit polyclonal antibodies directed against LGE2-protein adducts that form pyrroles, and alkaline phosphatase-conjugated polyclonal antibodies specific for apo B or apo (a). It demonstrates a high degree of specificity, sensitivity and validity. RESULTS: Epitopes characteristic for LGE2-pyrroles were quantified in patients with end-stage renal disease (ESRD) that had undergone continuous ambulatory peritoneal dialysis (CAPD) and in a gender- and age-matched control population. In addition to finding that both LDL and Lp(a) levels were elevated in CAPD patients, we also found that plasma Lp(a) but not LDL was more oxidized in CAPD patients when compared to corresponding lipoproteins from healthy subjects. Using density gradient ultra-centrifugation of plasma samples, we found that modified Lp(a) floats at the same density as total Lp(a). CONCLUSIONS: The results of this study demonstrate that oxidation of plasma Lp(a) is a characteristic of ESRD patients undergoing CAPD. This ELISA may be useful for further investigations on oxidation of lipoproteins in the circulation of specific patient populations.

Risk factors for peritonitis in long-term peritoneal dialysis: the Network 9 peritonitis and catheter survival studies. Academic Subcommittee of the Steering Committee of the Network 9 Peritonitis and Catheter Survival Studies.

To determine factors involved in peritoneal dialysis-associated peritonitis and catheter loss, all point prevalent peritoneal dialysis patients in Health Care Finance Administration (HCFA) end-stage renal disease (ESRD) Network 9 were followed throughout 1991 for peritonitis events and throughout 1991 to 1992 for catheter survival. Data were collected by questionnaires compiled by the dialysis facility and validated by network staff. Peritonitis was reported 1,168 times in 729 of the 1,930 patients. By gamma-Poisson regression, a significantly increased risk for peritonitis was observed for patients with previous peritonitis, black race, and those dialyzing with standard connectors or cyclers compared with disconnect systems. Decreased risks were observed for patients with longer ESRD experience and when prophylactic antibiotics were administered before catheter insertion. Postinsertion leakage, diabetes, visual problems, previous or current immunosuppression, and physical activity were not risk factors. Infection of any kind caused the removal of 68% of the 414 catheters lost. Patients with downward-directed tunnels were less likely to experience concomitant exit site/tunnel infections associated with peritonitis. Peritonitis episodes with Staphylococcus epidermidis-like organisms were more likely to resolve with a single course of antibiotics. Perhaps because of their higher infection rate, blacks were more likely than whites to use a disconnect system. In general, the outcome of peritonitis in blacks was similar to that in whites, except that blacks were less likely to be hospitalized and were less likely to die.

Effect of angiotensin-converting enzyme inhibition on nephropathy in patients with a remnant kidney.

OBJECTIVES: This study was performed to evaluate the effect of angiotensin-converting enzyme inhibitor (ACEI) therapy and dietary protein restriction on nephropathy involving a remnant kidney. METHODS: Five patients with proteinuria > or = 5 years following partial removal of a solitary kidney were treated with a low-protein diet and an ACEI agent. Four patients had biopsy-proven focal segmental glomerulosclerosis. The daily urinary protein excretion ranged from 1240 to 10,032 mg. The serum creatinine levels ranged from 1.2 to 3.1 mg/dL. RESULTS: The post-treatment follow-up interval ranged from 18 to 30 months. The treatment regimen was well tolerated in all patients. Four patients experienced a reduction in the urinary protein level while maintaining stable overall renal function. In 1 patient, the urinary protein level increased and renal function gradually deteriorated following ACEI therapy. CONCLUSIONS: These preliminary data suggest that ACEI therapy and a low-protein diet may mitigate nephropathy associated with a remnant kidney.

Lipid abnormalities and end-stage renal disease: implications for atherosclerotic cardiovascular disease?

Disorders of lipoprotein metabolism may have clinical implications as determinants of cardiovascular risk in patients with end-stage renal disease (ESRD). However, the role of hypertriglyceridemia or other parameters of lipoprotein metabolism as predictors of clinical measures of outcome during ESRD treatment is currently unknown. We determined the relationship between blood lipid, lipoprotein-cholesterol, apoprotein levels and the risk of cardiovascular death during 48 months of hemodialysis treatment in a prospective study of 129 patients with ESRD. Although serum triglyceride levels were increased in patients with preexisting cardiovascular disease, they were unrelated to clinical outcome during the period of follow-up. In contrast, lipoprotein(a) was an independent predictor of the risk of deaths attributable to cardiovascular disease during the prospective period of follow-up. Although these findings do not exclude the possibility that hypertriglyceridemic hemodialysis patients have atherogenic lipoproteins or associated metabolic conditions that predispose to cardiovascular death, our findings suggest that measurements of serum triglyceride concentration may not improve the cardiovascular risk assessment of hemodialysis patients.

Intermittent minibolus oral vitamin D3 in CAPD patients with resistant parathyroid hormone values.

Pulse vitamin D3 (3-5 micrograms po, twice a week) has been proposed for individuals with hyperparathyroidism resistant to daily po vitamin D3 therapy. While pulse vitamin D3 is effective, concerns regarding oversuppression of parathyroid hormone (PTH) values leading to adynamic bone disease have arisen. In view of these concerns, minibolus vitamin D3 po therapy was utilized in dosages varying from 0.25-1.0 micrograms twice a week in an effort to control elevated PTH values in patients who failed standard daily vitamin D3 therapy. Eleven patients were changed to minibolus vitamin D3 therapy from standard daily treatment (6 women, 5 men; mean age 55.8 +/- 14 years), on continuous ambulatory peritoneal dialysis (CAPD) for an average of 28.4 +/- 23 months. The mean intact PTH (iPTH) values on 0.25 microgram/day decreased by 54.5 +/- 167.8 pg/mL compared to pretreatment values. The mean iPTH on minibolus vitamin D3 therapy decreased by 165.1 +/- 104 pg/mL. The response to minibolus vitamin D3 was not truly predicted by the baseline PTH values. While the average decrease in PTH was greatest on 1.0 microgram two times a week, 2 patients experienced a decrease greater than 200 pg/mL in PTH on a lower dose. The greatest effect on PTH with minipulse vitamin D3 occurred when iPTH was < or = 500 pg/mL. While total calcium increased on daily vitamin D3, there was no significant change with minipulse therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Preserving renal function by revascularization.

Renal revascularization may improve or stabilize kidney function in properly selected patients with atherosclerotic renal artery stenosis. Determining kidney salvability, choosing the optimal form of intervention, and assessing preoperative risk are essential in approaching the treatment of this complex patient group.

Chronic glomerular microangiopathy complicating metastatic carcinoma.

Six cases of metastatic carcinoma associated with chronic glomerular microangiopathy and renal failure are reported. All had prominent subendothelial lucent zones and double-contoured glomerular basement membranes. There was no immunohistologic or ultrastructural evidence for immune complex entrapment in glomeruli. By immunohistology, material antigenically related to fibrin or fibrinogen was identified in glomerular basement membranes despite a paucity of typical fibrillar fibrin. Four patients received mitomycin C before the onset of renal disease, and one patient received chemotherapy other than mitomycin C before development of renal failure. One patient had no chemotherapy but was given radiotherapy, which did not include the kidneys in the irradiated field. These six cases emphasize the diverse pathophysiologic mechanisms by which glomerular microangiopathy may arise in metastatic carcinoma.

Prediction of outcome in acute renal failure.

In an attempt to predict outcome in acute renal failure (ARF) we have utilized multiple logistic regression to analyze clinical data from 151 patients with ARF seen over a 15-month period. Recovery of renal function occurred in 60% of patients with a 58% survival. Our analysis demonstrated sepsis, respiratory failure, and oliguria to be the major predictors of nonrecovery of renal function. A logistic equation was generated for prediction of outcome and was validated in a second independent group of patients with ARF. Prediction of outcome could be achieved with a sensitivity of 75% and a specificity of 80%. Maximum sensitivity (100%) was associated with a 17% specificity, while maximum specificity (98%) yielded a sensitivity of 20%.