[A delicate balance: Gitelman syndrome and gestational diabetes. A case report].

Gitelman's syndrome (GS) is a rare autosomal recessive disorder characterized by hypokalemia, hypomagnesaemia, metabolic alkalosis, hypocalciuria and secondary hyperaldosteronism. The impact of GS on pregnant patients is still not clear, despite the many clinical cases described in literature. In particular, there is no data on the development of gestational diabetes. Altered glucose metabolism and insulin sensitivity have recently been described in patients with GS. We describe here the clinical case of a young woman suffering from GS who started pregnancy and developed gestational diabetes. Our experience, while confirming the need of assiduous ionic monitoring especially in the first trimester of pregnancy, seems to help scaling down the maternal-fetal risk in patients suffering from GS. We also suggest the introduction of a low-glucose diet to prevent the onset of gestational diabetes, a condition burdened with severe complications. Finally, a reminder that drugs active on ionic balance must be of proven maternal and fetal safety.

Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

BACKGROUND: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. METHODS: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. RESULTS: In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods. CONCLUSIONS: Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

Effects of high-volume online mixed-hemodiafiltration on anemia management in dialysis patients.

BACKGROUND: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). METHODS: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models. RESULTS: Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687). CONCLUSIONS: Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.

Optimization of mid-dilution haemodiafiltration: technique and performance.

BACKGROUND: Mid-dilution haemodiafiltration (MD-HDF), reported as a highly efficient convective-mixed technique, has demonstrated serious drawbacks in relation to the high pressure originating inside the blood compartment of the filter during clinical application. This randomized crossover design study was planned to optimize the efficiency of the MD-HDF technique while reducing its inherent risks. METHODS: Fifteen patients on RRT were submitted in random sequence to standard and reverse MD-HDF under similar operating conditions. Efficiency in solute removal was evaluated by measuring urea (U), phosphate (P) and beta2-microglobulin (beta2-m), mean dialysate clearances (K(DQ)) and eKt/V. Blood and dialysate compartment pressures were monitored on-line during the sessions, and instantaneous hydraulic and membrane permeability indexes were calculated. RESULTS: During standard MD-HDF sessions, unlike with reverse MD-HDF, excessive blood inlet and transmembrane pressure prevented the planned infusion from being maintained. Resistance index and membrane permeability to water and middle molecules substantially improved with reverse MD-HDF. This resulted in higher beta2-m removal (221.3 +/- 81.3 versus 185.1 +/- 65.5 mg/session, P = 0.007). Phosphate removal was comparable, while U removal was greater with standard MD-HDF (K(DQ) 272 +/- 35 versus 252 +/- 29 ml/min, P = 0.002; eKt/V 1.63 +/- 0.23 versus 1.49 +/- 0.17, P = 0.005). CONCLUSIONS: This study demonstrated the ability of MD-HDF to remove significant amounts of medium-sized uraemic compounds and phosphate, but safe rheologic and hydraulic conditions were only maintained by carrying out treatments with the dialyser used in reverse configuration. For this purpose, the larger MD-220 dialyser ensured better tolerance together with higher middle molecules clearance, even though small molecule removal was slightly worsened. The results of this study may provide some insight into the complex interactions between pressures and flux within the original structure of MD-dialysers and help optimize the clinical application of the technique and reduce its risks.

New strategies in haemodiafiltration (HDF): prospective comparative analysis between on-line mixed HDF and mid-dilution HDF.

BACKGROUND: Improvement in the uraemic toxicity profile obtained with the application of convective and mixed dialysis techniques has stimulated the development of more efficient strategies. Our study was a prospective randomized evaluation of the clinical and technical characteristics of two new haemodiafiltration (HDF) strategies, mixed HDF and mid-dilution HDF, which have recently been proposed with the aim of increasing efficiency and safety with respect to the standard traditional HDF infusion modes. METHODS: Ten stable patients on renal replacement therapy (mean age 64.7 +/- 8.2 years) were submitted in randomized sequence to one mid-week session of mid-dilution HDF and one of mixed HDF with trans-membrane pressure feedback control. All sessions were carried out under similar operating conditions and involved monitoring pressure within the internal dialyser compartments and calculating the rheological and hydraulic indexes. Efficiency in removing urea, phosphate and beta2-microglobulin (beta2-m) was tested. RESULTS: In mixed HDF, safer and more effective flux/pressure conditions resulted in better preservation of the hydraulic and solute membrane permeability (mean in vivo ultrafiltration coefficient 36.9 +/- 3.9 vs 20.1 +/- 3.3 ml/h/mmHg) and ensured higher volume exchange (38.7 +/- 4.2 vs 35.3 +/- 6.5 l/session, P = 0.02) and greater efficiency in removing small and middle molecules (mean urea clearance: 274 +/- 42 vs 264 +/- 47 ml/min, P = 0.028; eKt/V: 1.78 +/- 0.22 vs 1.71 +/- 0.26, P = 0.036; mean phosphate clearance: 138 +/- 16 vs 116 +/- 45 ml/min, P = 0.2; mean beta2-m clearance: 81 +/- 13 vs 59 +/- 13 ml/min, P = 0.001). CONCLUSIONS: Mixed HDF was the most efficient technique in the highest range of safe operating conditions. In mid-dilution HDF, high pressures generated inside the dialyser compromised membrane permeability and limited the total infusion rate, resulting in an overall reduction in solute removal.

A high calcium-phosphate product is associated with high C-reactive protein concentrations in hemodialysis patients.

BACKGROUND: An elevated CaxPO4 product and C-reactive protein (CRP) have been associated with coronary artery calcification and increased cardiovascular mortality in hemodialysis (HD) patients. However, it has not been defined, so far, whether and how both parameters are related to each other. For this reason we have evaluated in a cross-sectional and in an interventional study the possible correlation between CaxPO4 and CRP and the effect of the correction of a high CaxPO4 on CRP levels. METHODS: 47 uremic patients (age 65 +/- 16 years) on regular chronic HD were selected from a total population of 125 prevalent patients treated at our Institution. Patients had no clinical evidence of either acute infectious or inflammatory diseases for at least 4 weeks before the study. They were on regular bicarbonate HD for 6-329 months (median 42). CRP, hemoglobin (Hb), serum albumin (sAlb), protein catabolic rate (PCRn), serum calcium (Ca), serum phosphorus (PO4), CaxPO4, intact PTH, Kt/V, presence of ischemic heart disease (IHD) and/or peripheral vascular disease (PVD) were recorded. CRP was Ln-transformed in all statistical analyses because of positive skewness. RESULTS: The main findings were: LnCRP 2.17 +/- 0.77 mg/l, Ca 10.1 +/- 0.4 mg/dl, PO4 5.8 +/- 0.6 mg/dl, CaxPO4 59 +/- 6 mg2/dl2, andPTHint 218 +/- 195 ng/ml. 18/47 had IHD, 18/47 PVD. A significant hyperbolic correlation between CaxPO4 and CRP was observed. A piecewise linear regression model analysis identified a break-point for CaxPO4 at 55 mg2/dl2. Comparison of CRP levels after the division of the patients into two groups according to CaxPO4 break-point (group A, CaxPO4 < or = 55 mg2/dl2, n = 16 patients; group B, CaxPO4 >55 mg2/dl2, n = 31 patients) showed that CRP levels were significantly lower in patients in group A (LnCRP 1.43 +/- 0.22 mg/l) than in group B (LnCRP 2.55 +/- 0.67 mg/l, p < 0.0001). Multiple regression analysis bearing LnCRP as dependent variable confirmed CaxPO4 as the most significant variable among the other variables examined. In 22 patients with CaxPO4 > or = 60 mg2/dl2, we performed intensive lowering of the CaxPO4 product in order to reach and maintain a CaxPO4 , or =55 mg2/dl2 for 3 months. At the end of observation, a significant reduction in CaxPO4 and LnCRP was observed (CaxPO4 pre 62.8 +/- 1.9 vs. post 46.3 +/- 6.2 mg2/dl2: p < 0.0001; LnCRP pre 2.32 +/-0.36 vs. post 1.83 +/- 0.14 mg/l: p < 0.0001). No significant variation in the other biochemical parameters was observed. CONCLUSIONS: Our data show that in chronic HD patients in steady clinical conditions with no clinical evidence of either infectious or inflammatory diseases, a high CaxPO4 is associated with high CRP concentrations. Intensive lowering of CaxPO4 reduces CRP