Nephron Clinical Practice最新文献

Background: Isotopic glomerular filtration rate (iGFR) measurement is comparable to the inulin method. In this study, we compared urinary and plasma iGFR methodologies in patients with diabetic nephropathy.

Methods: A total of 147 patients from 3 sites in the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at baseline, 18 and 36 months.

Results: The mean (with standard deviation) plasma iGFR of 60.7 (24.9) ml/min/1.73 m(2) compared to urinary iGFR of 52.0 (28.0) ml/min/1.73 m(2) was statistically significant (p value <0.001). Although plasma and urinary iGFRs were highly related (R(2) = 0.86), plasma iGFR increasingly overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional analyses, the two measures of iGFR were weakly related (R(2) = 0.32) in regard to patients' change over 18 months of follow-up.

Conclusion: Plasma iGFR may not be a suitable method for accurately measuring GFR in patients with advancing degrees of chronic kidney disease from diabetic nephropathy.

Background: Hemodialysis (HD) patients are exposed to a high risk of death. Nutritional status has been recognized as a key factor for patient survival. Nutritional markers have been shown to improve after HD onset. In this study we have analyzed the dynamics of target weight (TGW) change and the evolution of other nutritional parameters during the first year of HD treatment and their influence on patients' outcomes.

Methods: We have analyzed a retrospective cohort of incident patients starting HD therapy between January 2000 and January 2009, and studied the values and changes in TGW, interdialytic weight gain (IDWG), predialysis systolic blood pressure, serum albumin, protein intake, C-reactive protein (CRP) from the start and first week (W1), W8, W12, W26 and W52 in patients who survived the first year of therapy. We have analyzed the relationship between TGW changes with other nutritional parameters and the patient survival.

Results: Among the cohort including 363 patients starting HD therapy, 251 (age 65.8 ± 14.8 years, 93 female/158 male, diabetes 36%) survived at least 1 year after dialysis onset and were followed for 44.9 months. During the first 8 weeks, the TGW decreased by 6.5 ± 5.6% (initial TGW change). The initial TGW change was correlated with IDWG at W12 and W26, and with changes in serum albumin and nPNA (normalized protein equivalent of nitrogen appearance) between HD W1 and W52 (respectively +7.8 and +11.4%). From W8 to W52, the TGW increased by +1.9 ± 7.4% (secondary TGW change). The Kaplan-Meier analysis displayed a significantly better survival in patients above the median (+2.3%) of the secondary TGW change (respectively -3.6 ± 5.2% and +7.6 ± 4.5%). The two groups above and below this median were not different according to age, diabetes or cardiovascular event history but the patients above the median had a significant higher IDWG and protein intake. In the Cox model analysis the patient overall mortality was related to age (p < 0.0001), to the secondary TGW change (p = 0.0001), and to the CRP level at W52 (p < 0.0001).

Conclusions: The initial fluid removal was related to nutritional markers. The secondary TGW change during the first year of HD treatment calculated after the initial phase of fluid removal was identified as a strong predictor of survival. It was associated with a better food intake whereas the patient case mix was not different. These data highlight the importance of nutrition and food intake in the first year of dialysis therapy and the need for nutritional follow-up and support in incident HD patients. It stresses the need in understanding the key factors associated with food intake in this setting.

Background: We compared myocardial perfusion in patients first on conventional hemodialysis (HD) and then on hemodiafiltration (HDF).

Methods: Myocardial perfusion scintigraphy was performed in 25 patients pre- and post-HD. Patients were then converted to HDF for 3 months prior to repeating the scintigraphy. (99m)Tc-methoxyisobutylisonitrile was administered intravenously pre-dialysis and then within the last hour of dialysis. Up to 90 min after injection, tomographic images were obtained. Clinical and laboratory data were collected pre- and post-dialysis.

Results: Five patients did not complete the study. Patients entering the study were on average 41.7 years old and on HD for 4 years (median). The mean standard Kt/V for the two procedures was not statistically different (1.55 for HD and 1.48 for HDF). The mean substitution volume for HDF was 18.48 liters. There were no significant differences in changes in blood pressures between HD and HDF (p = 0.22). There were no significant differences in myocardial perfusion defects in patients on HD compared with those on HDF. During dialysis in both studies, the data showed a general trend to worsening of perfusion defects.

Conclusions: There was no advantage of HDF over HD with no statistical difference in perfusion defects between HD and HDF. There was a trend to worsening of perfusion defects during dialysis in the majority on HD and HDF. Midweek dialysis perfusion scores appeared to be consistently lower than early-week dialysis, but this was not statistically significant. The pathogenesis of the defects may lie at a microcirculatory level.

Background: Dose requirements of erythropoietin-stimulating agents (ESAs) can vary considerably over time and may be associated with cardiovascular outcomes. We aimed to longitudinally assess ESA responsiveness over time and to investigate its association with specific clinical end points in a time-dependent approach.

Methods: The German Diabetes and Dialysis study (4D study) included 1,255 diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those patients, the erythropoietin resistance index (ERI) was assessed every 6 months during a median follow-up of 4 years. The association between the ERI and cardiovascular end points was analyzed by time-dependent Cox regression analyses with repeated ERI measures.

Results: Patients had a mean age of 66 ± 8.2 years; 53% were male. During follow-up, a total of 495 patients died, of whom 136 died of sudden death and 102 of infectious death. The adjusted and time-dependent risk for sudden death was increased by 19% per 5-unit increase in the ERI (hazard ratio, HR = 1.19, 95% confidence interval, CI = 1.07-1.33). Similarly, mortality increased by 25% (HR = 1.25, 95% CI = 1.18-1.32) and infectious death increased by 27% (HR = 1.27, 95% CI = 1.13-1.42). Further analysis revealed that lower 25-hydroxyvitamin D levels were associated with lower ESA responsiveness (p = 0.046).

Conclusions: In diabetic dialysis patients, we observed that time-varying erythropoietin resistance is associated with sudden death, infectious complications and all-cause mortality. Low 25-hydroxyvitamin D levels may contribute to a lower ESA responsiveness.

Background/aims: Bone fracture is often complicated in hemodialysis (HD) patients. Metabolic acidosis is related to bone disease and muscle wasting, but it is not known whether acid-base disturbance is associated with the risk of bone fractures. The aim of this study was to clarify the association of serum bicarbonate level with bone fracture in HD patients.

Methods: Using a subcohort of the Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D), 890 prevalent HD patients (age: 62 years old, male: 62.8%, duration of dialysis: 8.3 years) with secondary hyperparathyroidism were studied. After measuring predialysis serum bicarbonate at a 2-day interdialytic interval, we prospectively followed them every 3 months, and examined the occurrence of any type of bone fracture or hospitalization due to fracture over a 3-year observation period.

Results: Seventy-four bone fractures and 47 hospitalizations due to fracture were observed during the follow-up period. HD patients with serum bicarbonate <20 mmol/l had a 1.93 (95% CI 1.01-3.71)-fold higher risk for all-cause fractures than those with serum bicarbonate of 20.0-21.9 mmol/l. A higher bicarbonate level (≥22 mmol/l) was also related to an increased risk of bone fracture. A restricted cubic regression spline disclosed that the higher or the lower than 21.0 mmol/l of serum bicarbonate, the greater the risk for bone fracture.

Conclusion: Both a lower level and a higher level of predialysis bicarbonate concentration were associated with risk of bone fracture in HD patients with secondary hyperparathyroidism.

The introduction of cyclophosphamide and high-dose glucocorticoids for anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) has allowed a reduction in 1-year mortality from 80% to 10-20%. AAV is now a chronic disease, and greater emphasis has turned to improving treatment-related toxicity, reducing relapses and providing alternative treatments for refractory disease. Rituximab, an anti-CD20 B cell-depleting therapy, has been used for over a decade in patients with AAV. Rituximab offers a significant advance in the treatment of these diseases. It has an established role for remission induction and is now being investigated as a remission maintenance agent. For remission induction, randomised trials have reported similar remission rates with rituximab and cyclophosphamide, and rituximab is now an approved alternative to cyclophosphamide in severe AAV. In clinical practice, rituximab is increasingly used for refractory and relapsing disease. Further remission induction data with rituximab for life-threatening renal and pulmonary disease may be provided by the ongoing PEXIVAS trial (NCT00987389). With standard therapies, 50% of patients with newly diagnosed AAV relapse by 5 years. Relapses are higher still in patients with known relapsing disease. For remission maintenance, treatment trials are comparing repeat rituximab dosing to azathioprine. The MAINRITSAN trial (NCT00748644) included mainly newly diagnosed AAV patients following cyclophosphamide induction therapy. The RITAZAREM trial (NCT01697267) is randomising patients with relapsing disease after rituximab induction therapy. Preliminary results with rituximab maintenance therapy are encouraging, although the optimal dosing regimen and duration has yet to be defined. Other areas for further investigation include remission maintenance therapy requirement after rituximab induction in newly diagnosed AAV, and the role of rituximab in eosinophilic granulomatosis with polyangiitis where no randomised data exists.

Background: Leukocytosis is a powerful predictor of incident chronic kidney disease (CKD) and related outcomes. However, the association between periodontitis measures and increased leukocytosis in the context of CKD has not been well described. We sought to identify which individual measures of periodontal disease may best associate with reduced estimated glomerular filtration rate (eGFR) and albuminuria, and to test if these measures were associated with increased leukocytosis in subjects with established CKD.

Methods: We estimated, among 13,270 participants in the National Health and Nutrition Examination Survey III study, the associations between case-based definition of periodontitis, clinical attachment loss (CAL) and pocket depth (PD) as individual measures of periodontal disease, with renal function measures and leukocytosis.

Results: In adjusted multivariate analyses, case-based definition of severe periodontitis was associated with albuminuria (β = 0.003, p = 0.01) but not with eGFR. However, CAL and PD were all individually associated with both albuminuria (β = 0.08, p < 0.001 and β = 0.06, p < 0.001, respectively) and eGFR (β = -0.05, p < 0.001 and β = -0.03, p < 0.001, respectively). We found significant associations between elevated CAL and PD with leukocytosis. Lastly, we found a marked association between the joint presence of CKD and elevated CAL or PD with leukocytosis (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4-7.5 and OR 3.2, 95% CI 1.1-9.7, respectively).

Conclusion: Individual measures of periodontal disease are associated with renal function and heightened leukocytosis in CKD subjects. The significantly added inflammatory burden noted in CKD subjects with periodontal disease argue for targeting periodontitis treatment as part of our multifaceted approach to CKD patients.

The major advances achieved in immunology and cellular biology have led to the development of biotherapies that specifically target different mediators and pathways involved in the physiopathology of renal diseases. After the major breakthroughs obtained with B-cell depletion in autoantibody-mediated glomerulopathies, several other immunomodulation strategies are being tested in autoimmune glomerulonephritides, such as blockade of B-cell costimulation and activation, inhibition of complement pathways or modification of the T-B-lymphocyte crosstalk. Other drugs, inhibiting proinflammatory cytokines, are being developed in order to control the inflammatory response initiating and amplifying the kidney tissue injury observed in different systemic diseases. Finally, several promising therapeutic agents target specific renal cells such as podocytes or fibroblasts, blocking the common final steps of the deleterious pathological process underlying various types of nephropathy. Although several of these drugs are still under evaluation in phase 2/3 clinical trials, biotherapies have undoubtedly opened a new era in the treatment of glomerular disease.

Dietary management of chronic kidney disease (CKD) focusses on limiting the intake of substances that might accumulate to toxic levels (such as potassium, phosphorus or salt) and, although still a matter of debate for some, restricting dietary protein to retard kidney damage. Recent evidence brings the opportunity to revisit the role of a healthy diet on disease progression and on some of the cardiometabolic complications of moderate/advanced CKD, such as inflammation or oxidative stress control. This review provides a brief overview of dietary strategies that delay CKD progression and CKD complications, and discusses currently limited data addressing the development of malnutrition and protein-energy wasting before dialysis initiation.