Massimo Morosetti

Automatic Adaptive System Dialysis for Hemodialysis-Associated Hypotension and Intolerance: A Noncontrolled Multicenter Trial

BACKGROUND Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.

Oxidative damage to RBC membranes and pentose phosphate shunt activity in hemodialysis patients after suspension of erythropoietin treatment

During follow-up of anemic hemodialysis patients (HDP) treated with recombinant human erythropoietin (rHuEpo), it was noticed that in five HDP, some time after suspension of rHuEpo, hemoglobin (Hb) levels remained at acceptable levels. A metabolic block of the pentose phosphate shunt (PPS) has been described in HDP, which leads to increased oxidative damage of red blood cell (RBC) membranes and increased susceptibility to hemolysis. The increased production of short-chain fatty aldehydes, including malonyldialdehyde (MDA), is an appropriate index of oxidative damage. This study aimed to verify whether the maintenance of acceptable levels of Hb was related to a change in RBC membrane oxidative damage and pentose phosphate shunt activity. In the five HDP in question who required rHuEpo (150 U/kg/week) for severe anemia (Hb = 7.48 +/- 0.95 g/dl), after a stable level of Hb > 10 g/dl was reached for at least 1 month, rHuEpo treatment was stopped. Hb levels remained adequate (Hb = 10.68 +/- 0.77 g/dl) after 14.6 +/- 7.64 months. The oxidative damage was evaluated by measuring RBC MDA (microgram/ml packed RBC) basal levels, and PPS activity by measuring MDA levels after incubation with ascorbate and cyanide (delta % RBC MDA production). Ten anemic HDP not treated with rHuEpo were used as controls (Hb = 8.12 +/- 1.32 g/dl). It was found that the maintenance of adequate levels of serum Hb after suspension of rHuEpo therapy is related to a decrease in RBC membrane oxidative damage (RBC MDA HDP = 2.40 +/- 0.41 vs. RBC MDA controls = 18.23 +/- 6.56; P < 0.005) in consequence of the normalization of pentose phosphate shunt activity.

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study

Abstract Background and objectives: Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study. Materials and Methods: In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective. Results: Four cohorts were identified: patients treated with oral (PO) calcitriol (n = 182), intravenous (IV) calcitriol (n = 34), IV paricalcitol (n = 62), and IV paricalcitol + cinacalcet therapy (n = 20); the cinacalcet monotherapy group was not analysed due to low number of patients (n = 9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300 pg/ml; p < 0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol + cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort’s PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p = 0.020, p = 0.012, and p = 0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol + cinacalcet cohort (p < 0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns. Conclusions: The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol + calcimemtics (p < 0.001), without a significant difference in terms of baseline severity and PTH control.

Cardiac Function and Oxygen Balance in Septic Patients during Continuous Hemofiltration

The aim of this work was to study hemodynamic, oximetric and metabolic parameters in septic patients during continuous hemofiltration, in order to determine whether the changes in hemodynamic parameters can influence the oxygen utilization in peripheral tissues. 29 multiple organ failure patients with septic shock were studied during the first 48 h of continuous hemofiltration: 18 were submitted to CAVH and 11 patients were treated with CAVHD to correct ARF and fluid overload. Our data show that RVEF improves and REDVI reduces progressively during treatment, together with a significant reduction of the cardiac index after 48 h of CAVH(D). There were no significant variations in oxygen tissue parameters, while plasma lactate was reduced significantly. In conclusion, our data confirm that continuous hemofiltration may be useful in septic patients to correct fluid overload and ARF, without affecting hemodynamic stability and oxygen balance. Moreover, in septic patients, this technique improves hemodynamics, reduces the filling pressure in the right heart and reduces hyperdynamic response as CI and SVRI, without any negative effects on O2 balance.

Disappearance of oxidative damage to red blood cell membranes in uremic patients following renal transplant.

Hemodialysis patients display increased oxidative damage to red blood cell (RBC) membranes, characterized by elevated levels of malonyldialdehyde (MDA), a short chain aldehyde produced by the oxidation of the polyunsaturated fatty acids (PUFA) in the RBC membranes. This is the result of a metabolic blockage of the pentose-phosphate shunt in uremic patients, which causes reduced detoxification of highly oxidative free radicals. The oxidative damage induces increased RBC rigidity and decreased RBC deformability, therefore favoring hemolysis. The aim of this work was to determine if a functioning renal graft would restore normal erythrocyte metabolism, reducing the oxidative damage. To this end, we have determined RBC MDA concentrations in 20 hemodialysis (HD) patients (RBC MDA 18.22 +/- 4.36 micrograms/ml packed RBC), 20 renal transplant (T) patients with well functioning grafts (serum creatinine less than 2 mg%) (RBC MDA 1.2 +/- 0.4 micrograms/ml packed RBC) (T vs. HD P less than 0.005) and 20 healthy controls (HC) (RBC MDA 1.44 +/- 0.6 micrograms/ml packed RBC) (HC vs. HD P less than 0.005; HC vs. T NS). Our findings show that a well-functioning renal graft restores normal RBC metabolism and eliminates the oxidative damage induced by uremia.

Extracapillary proliferation is an independent predictive factor in Immunoglobulin A nephropathy

Oxford classification of Immunoglobulin A Nephropathy (IgAN) identifies four pathological features as predictors of renal outcome (MEST‐score): mesangial proliferation (M); endocapillary proliferation (E); segmental glomerulosclerosis (S); tubular atrophy/interstitial fibrosis (T). In particular extracapillary proliferation (Ex) was not considered as an independent histological variable predicting renal outcome. Recently the VALIGA study provided a validation of the Oxford classification in a large European cohort of IgAN patients and re‐stated that Ex is not associated with a worse renal prognosis. We propose a retrospective study to evaluate the predictive value of the MEST‐score in a multi‐centre, single region group of patients from central Italy and in addition, to investigate Ex as a marker predicting renal outcome.

Clinical management of nondialysis patients with chronic kidney disease: a retrospective observational study. Data from the SONDA study (Survey Of Non-Dialysis outpAtients)

Background A lack of awareness of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. Purpose The objective of this study was to assess the therapeutic management and outcome of nondialysis CKD patients. Methods Three hundred ninety-seven patients (54.9% males aged 67.5 ± 14.6 years) were retrospectively screened at the Nephrology Department, GB Grassi Hospital, Rome, Italy. After a baseline visit, patient data were collected every 6 months for a total of 24 months. Clinical characteristics were measured at baseline, then the following outcomes were measured every 6 months: staging of CKD, presence of concomitant diseases, treatment and adherence to Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for anemia management. Results Three hundred sixty-eight (92.7%) patients attended at least one visit and 92 (23.2%) patients attended all four visits. Patients were mainly referred to a nephrologist for chronic renal failure (61.7%) or hypertension (42.8%). At baseline, 79.6% of patients had previous hospitalization and 79.1% were receiving antihypertensive medication. Serum creatinine and/or glomerular filtration rate was examined in >90% of patients, whereas parathyroid hormone was rarely examined (5.5%). Vitamin D supplementation was received by 6.5% of patients. The majority of patients were staged at 3 or 4 CKD (32% and 23.9%, respectively) and did not significantly change over time. The use of antithrombotic, antilipidemic and erythropoietin medication increased over the four surveys. The majority of patients (86.8%) achieved hemoglobin K/DOQI target levels. Conclusion These findings demonstrate a current lack of attention of CKD and related disorders (mineral metabolism, electrolyte balance, and anemia) at the level of the general practitioner (GP) and non-nephrology specialist, which can result in both delayed referral and inadequate treatment. By increasing both awareness of CKD and the coordinated relationship between GPs and nephrologists, patient clinical and therapeutic outcome may be improved.

Renal Functional Reserve (RFR) in Patients with Short Term Type 1 Diabetes Mellitus (DM1) without Nephropathy

Unlike type 2, type 1 diabetes mellitus is associated with a higher risk of increased Glomerular Filtration rate (GFR) and glomerulopathy. Clinical studies have indicated that GFR increases after a protein load in healthy volunteers (RFR). The aim of the present study was to verify the existence of the RFR in DM1 pts. Our results suggest that well controlled short term DM1 pts show a normal response to protein loading as healthy subjects.