Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The "old" cross-talk between kidney and bone (classically known as "renal osteodystrophies") has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of "osteoporosis" emerges in nephrology as a new possibility "if results will impact clinical decisions". Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

What infusion flow should be used for mid-dilution hemodiafiltration?

BACKGROUND: There is still no consensus on the optimal infusion flow (Qi) in mid-dilution hemodiafiltration. The aim of this study was to compare mid-dilution with varying Qi. SUBJECTS AND METHODS: Prospective study in 25 patients who underwent seven hemodialysis sessions with a Qi of 0, 50, 100, 150, 200, 250 and 300 ml/min. RESULTS: All sessions were well tolerated except Qi 300 ml/min. No significant differences in urea, creatinine, alpha(1)-microglobulin or alpha(1)-acid glycoprotein reduction ratios were observed. beta(2)-Microglobulin, myoglobin and prolactin reduction ratios were higher with Qi 150, 200, 250 and 300 ml/min in comparison with Qi of 0, 50 and 100 ml/min. There were no differences in the removal of small or larger molecules when Qi was 150 ml/min or higher. CONCLUSIONS: Optimal Qi in mid-dilution appears to be in the range of 150-250 ml/min since good clinical outcomes, similar efficiency and no technical complications up to a Qi of 250 ml/min were observed.

Optimization of dialysate flow in on-line hemodiafiltration.

INTRODUCTION: Currently, on-line hemodiafiltration (HDF-OL) is the most effective technique. Several randomized studies and meta-analyses have shown a reduced mortality and a direct association with convective volume has been reported. At present, it has not been established if an increased dialysate flow (Qd) results in improved results in terms of convective and depurative efficiency. We aim at assessing the effects of Qd variations on convective volume and its depurative capacity in patients on HDF-OL. MATERIAL AND METHODS: A total of 59 patients (45 men and 14 women) from a HDF-OL programme in which a monitor 5008 Cordiax with self-replacement was used, were enrolled. Patients were assessed in 5 sessions with post-dilutional HDF-OL, using helixone-based dialyzers, with only Qd being changed (300, 400, 500, 600 and 700ml/min). Serum levels of urea (60Da), creatinine (113 Da), ß2-microglobulin (11,800Da), myoglobin (17,200Da) and α1-microglobulin (33,000Da) were measured at the beginning and at the end of each session, in order to estimate the percent reduction of such solutes. RESULTS: An increased dialysate volume per session was observed, from 117.9±6.4 L with Qd 300ml/min to 232.4±12 L with Qd 700ml/min. No changes were found in replacement volume or convective volume. Regarding diffusion, Qd increase was associated to a significantly increased dialysis dose, with an increased Kt from 68±6.9 L with Qd 300ml/min to 75.5±7.3 L with Qd 700ml/min (p<0,001), and a gradually increased percent reduction in urea associated to increased Qd with significantly lower levels being found with Qd 300ml/min. No changes were found in other measured substances. CONCLUSION: Qd variations in HDF-OL do not change convective volume. A higher Qd was associated to a slightly increased urea clearance with no change being observed for medium and large molecules. Qd optimisation to the minimal level assuring an adequate dialysis dose and allowing water and dialysate use to be rationalised should be recommended.

Assessment of dialyzer surface in online hemodiafiltration; objective choice of dialyzer surface area.

INTRODUCTION: Online hemodiafiltration (OL-HDF) is currently the most effective technique. Several randomized studies and meta-analyses have observed a reduction in mortality as well as a direct association with convective volume. Currently, it has not been well established whether a larger dialyzer surface area could provide better results in terms of convective and depurative effectiveness. The aim of this study was to assess the effect of larger dialyzer surface areas on convective volume and filtration capacity. MATERIAL AND METHODS: A total of 37 patients were studied, including 31 men and 6 women, who were in the OL-HDF program using a 5008 Cordiax monitor with auto-substitution. Each patient was analyzed in 3 sessions in which only the dialyzer surface area varied (1.0, 1.4 or 1.8 m(2)). The concentrations of urea (60 Da), creatinine (113 Da), ß2-microglobulin (11800 Da), myoglobin (17200 Da) and α1-microglobulin (33000 Da) were determined in serum at the beginning and end of each session in order to calculate the percent reduction of these solutes. RESULTS: The convective volume reached was 29.8 ± 3.0 with 1.0 m(2), 32.7 ± 3.1 (an increase of 6%) with 1.4 m(2), and 34.7 ± 3.3 L (an increase of 16%) with 1.8 m(2) (p<.001). The increased surface of the dialyzer showed an increase in the dialysis dose as well as urea and creatinine filtration. The percentage of ß2m reduction increased from 80.0 ± 5.6 with 1.0 m(2) to 83.2 ± 4.2 with 1.4 m(2) and to 84.3 ± 4.0% with 1.8 m(2). As for myoglobin and a1-microglobulin, significant differences were observed between smaller surface area (1.0 m(2)) 65.6 ± 11 and 20.1 ± 9.3 and the other two surface areas, which were 70.0 ± 8.1 and 24.1 ± 7.1 (1.4 m(2)) and 72.3 ± 8.7 and 28.6 ± 12 (1.8 m(2)). CONCLUSION: The 40% and 80% increases in surface area led to increased convective volumes of 6 and 16% respectively, while showing minimal differences in both the convective volume as well as the filtration capacity when the CUF was higher than 45 ml/h/mmHg. It is recommended to optimize the performance of dialyzers with the minimal surface area possible when adjusting the treatment prescription.

On-line haemodiafiltration with auto-substitution: assessment of blood flow changes on convective volume and efficiency.

INTRODUCTION: On-line haemodiafiltration (OL-HDF) is currently the most effective technique and several randomised studies and meta-analyses have seen a reduction in mortality and an association directly related with convective volume is observed. Blood flow (Qb) limits the infusion rate to 25-33 % and is the main limiting factor for reaching an optimum substitution volume. With the recent incorporation of monitors with auto-substitution systems, the aim of the study was to assess the effect of Qb variations on convective volume and purifying capacity. MATERIAL AND METHODS: 23 patients, 17 men and 6 women, were included, with an average age of 65.5 ±10 years, time on dialysis 292.2 ± 15 minutes, which were in the OL-HDF programme with the 5008 Cordiax monitor with auto-substitution. Each patient was analysed over 5 sessions in which only the Qb was changed (250, 300, 350, 400 and 450 ml/min). In each session the substitution volume, total convective volume and parameters of dialysis were measured. The concentration of urea (60 Da), creatinine (113 Da), β2-microglobulin (11,800 Da), myoglobin (17,200 Da), prolactin (23,000 Da), α1-microglobulin (33,000 Da) and α1-acid glycoprotein (40,000 Da) in plasma was measured at the start and end of each session in order to calculate the percentage of reduction of these solutes. RESULTS: The trans-membrane pressure was less, with Qb 250 ml/min. A significant increase in convective volume was observed with the increase in Qb, 23.7, 26.9, 30.2, 32.8 and 35.2 l/session to 250, 300, 350, 400 and 450 ml/min, respectively (P < 0.001), representing a percentage of total purified blood of 33.2, 31.2, 30.2, 28.7 and 27.3 % respectively. The percentages of reduction of urea and creatine progressively increased with Qb, slight differences were observed with β2-microglobulin and myoglobin, and no changes were observed in the larger molecules. CONCLUSION: For each 50 ml/min increase in Qb, the convective volume increased by between 8 and 12 ml/min. The auto-substitution system strengthens the lowest Qbs in the percentage of convective volume with regards to total purified blood. Qb increases the purifying capacity of small molecules, favouring that of β2-microglobulin and myoglobin, and does not influence molecules of a greater molecular weight. 

Practical utility of thermodilution versus doppler ultrasound to measure hemodialysis blood access flow.

INTRODUCTION: The current clinical guidelines recommend indirect access blood flow (Qa) measurement as one of the most important components in vascular access maintenance programs. The best-know methods are doppler ultrasound (DU) and saline dilution method. OBJECTIVE: This study evaluates the efficiency of Qa measurement with thermodilution method (TD) in comparison with the DU. MATERIAL AND METHODS: Transversal study in 64 patients in hemodialysis (41 men); mean age 59.9 years with 54 AVFs and 10 PTFE. Qa reference value was obtained with DU in brachial artery (AVFs) or at the zone of arterial puncture (AVGs). Bland-Altman and interclass correlation coefficient (ICC) were used to study accuracy. RESULTS: Mean values obtained with DU-Qa were 1426 ± 753 mL/min AVFs and 1186 ± 789 mL/min AVGs. The mean Qa with TD was 1372 ± 770 AVFs (bias 54.6; ICC 0.923) and 1176 ± 758 AVGs (bias 10.2; ICC 0.992). In the subgroup of 28 patients with radiocephalic latero-terminal AVFs the DU-Qa was 1232 ± 767 mL/min. The Qa was in radial artery 942 (ICC 0.805); radial-ulnar artery 1103 (ICC 0.973); cephalic vein 788 (ICC 0.772) and TD 1026 (ICC 0.971). We detected 5 cases of significant stenosis. After endovascular treatment the Kt was 79 liters (61; p=0.043) and TD-Qa 895 mL/min (663; p=0.043). CONCLUSIONS: TD represents a good indirect method of Qa measurement. In the subgroup of patients with radiocephalic AVFs, Qa measurements in the radial and ulnar artery are more accurate. Therefore, in this situation the TD method obtained an excellent correlation in comparison to brachial artery.

Urgent pneumococcal urinary antigen, importance in the diagnosis of acquired pneumonia in HIV-1 patients.

The aim of our study was to determine the usefulness of pneumococcal urinary antigen (UA) collected in the emergency department (ED) for the microbiologic diagnosis of community-acquired pneumonia (CAP) in HIV patients and to compare it with other diagnostic tests. Prospective study from 1 January 2007 to 31 December 2008 included HIV-infected patients admitted at the ED with respiratory symptoms and who were diagnosed of CAP. UA, two blood cultures and sputum sample for culture determination were collected from every patient. Sixty-four patients were included. The mean age was 42 years. A total of 31 (48%) UA tests, 12 (19%) blood cultures and 21 (33%) sputum cultures tested positive. A microbiological diagnosis was obtained in 38 (59%) cases. Pneumococcal pneumonia was diagnosed in 32 cases. The statistical analysis showed that the test with best performance was the UA, both in relation to blood and sputum cultures (P<0.05). Two patients died during hospitalization (series mortality of 3%). In conclusion, given its good diagnostic performance, UA should be requested in the ED for the aetiological diagnosis of CAP.