Cesare Guarena

Acute Effects of Hemodialysis on Erythrocyte Sodium Fluxes in Uremic Patients

The acute effects of both acetate and bicarbonate hemodialysis on erythrocyte transmembrane sodium fluxes were investigated in 15 patients with chronic uremia. We observed a significance (p less than 0.01) stimulation of the Na+,K+ pump in both procedures, with a significant correlation to the amount of fluid removed during hemodialysis (r = 0.56, p less than 0.03). Outward Na+ cotransport fluxes significantly rose (p less than 0.05) after acetate hemodialysis and decreased (p less than 0.05) after bicarbonate hemodialysis. Minor and not significant pre- and posthemodialysis bidirectional changes were observed as regards the intraerythrocyte Na+ and K+ concentration, passive Na+ and K+ permeability, and Na+,Li+ countertransport. Hemodialysis may acutely affect the erythrocyte sodium pump and cotransport fluxes, possibly through the modulation of hormonal factors triggered by the extracellular volume changes.

Mitochondrial neurogastrointestinal encephalomyopathy treated with peritoneal dialysis and bone marrow transplantation

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by thymidine phosphorylase deficiency which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). It lacks an established treatment and the prognosis is traditionally poor. We report a case of a young female patient with normal renal function and MNGIE treated by peritoneal dialysis (PD) and allogeneic bone marrow transplantation (BMT). PD was effective in reducing dThd and dUrd plasma levels and in improving clinical symptoms. To our knowledge, this is the first report on the beneficial effects of PD regarding MNGIE neurological symptoms. PD, therefore, should be considered especially in medically compromised patients as a supportive treatment to improve clinical conditions before BMT.

Sodium-Lithium Countertransport Activity in Red Blood Cells of Patients With IgA Nephropathy

In this paper we report some results of our studies on patients with immunoglobulin (Ig)A nephropathy regarding (1) the familiar aggregation of erythrocyte sodium-lithium (Na,Li) countertransport; (2) the association of Na,Li countertransport with the presence of arterial hypertension and lipid abnormalities; (3) the correlation between Na,Li countertransport activity and renal functional reserve; and (4) the preliminary results of a longitudinal study. In 13 families of patients with IgA nephropathy, selected because both parents were available, we found a significant correlation between midparent and offspring Na,Li countertransport activity (Spearmans rank correlation = 0.65; P = 0.023), but no husband-wife relationship. In 49 patients, the activity of Na,Li countertransport was significantly higher in erythrocytes from 20 hypertensive patients than from either 29 normotensive patients or from 36 healthy age- and sex-matched normal subjects. Hyperlipidemic patients had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic patients and controls. In 17 patients a significant inverse correlation was found between the peak variation of creatinine clearance over baseline value after an oral protein load and the erythrocyte Na,Li countertransport activity (Spearman r = 0.54; P = 0.03). In a longitudinal study of 36 patients followed from 12 to 36 months, those showing a progression toward renal failure had an erythrocyte Na,Li countertransport activity higher than median value. The results of our studies show that in patients with IgA nephropathy a high erythrocyte Na,Li countertransport rate, genetically determined, is associated with the presence of arterial hypertension and lipid abnormalities, and perhaps with a less favorable disease outcome.

Verapamil in Arterial Hypertension with Renal Disease

Dr. Roberto Boero, Divisione di Nefrologia e Dialisi, Nuova Astanteria Martini,, Piazza Donatore di Sangue 3, I-10154 Torino (Italy) Dear Sir, Calcium antagonist drugs have been proved effective in the treatment of essential hypertension [1]. However, information regarding the hypotensive effect of these drugs in hypertensive patients with chronic renal disease is scanty; recently two papers appeared concerning the use of nifedi-pine in these patients [2,3]. We report our experience on the renal and antihypertensive effects of the calcium entry blocker verapamil in a slow-release preparation (Isoptin Retard®; Knoll AG) in a group of patients with hypertension secondary to renal parenchymal disease. We investigated 9 patients (6 males, 3 females). The mean age was 44 years (range 24–55 years). The diagnosis of renal disease was chronic interstitial nephritis in 6 cases, polycystic kidney disease in 2, and chronic glomerulonephritis in 1. Six had a creatinine clearance below 80 ml/min (serum creati-nine ranging from 1.5 to 3.4 mg/dl). After 2 weeks of placebo washout, the patients received verapamil retard for 4 weeks, starting with 120 mg twice daily. If the diastolic blood pressure was > 95 mm Hg after the first 2 weeks, verapamil retard was increased to 240 mg twice daily. After the placebo period and the first 2 weeks of treatment, effective renal plasma flow was evaluated, as well as the I-hippuran clearance [4]. The main results are shown in table I; in 4 cases the dosage of verapamil was increased to 480 mg/day. The heart rate did not change significantly during the study. The glomerular filtration rate, as assessed by the endogenous creatinine clearance, was not significantly modified, even in patients with impaired renal function. The drug was well tolerated: no adverse effect emerged on atrioventricular conduction and cardiac function; only 2 patients complained of mild constipation. Our results demonstrate that verapamil exerts a good antihypertensive effect, even in mild to moderate hypertension secondary to renal parenchymal disease. Moreover, in spite of blood pressure reduction, no adverse effect on renal hemodynamics was observed: in fact the renal plasma flow was maintained or slightly increased in Table I. Antihypertensive and renal effects of verapamil retard (mean ± SE) Placebo Verapamil retard 2 weeks 4 weeks

Pathogenesis of arterial hypertension in chronic uraemia: the role of reduced Na,K-ATPase activity.

In 38 uraemic dialysed patients (17 normotensive, 21 hypertensive) we measured (1) erythrocyte sodium concentration [Na] and ouabain-sensitive sodium efflux, and (2) arterial pressure, cardiac index and total peripheral resistance. Erythrocyte Na—K pump activity was lower in hypertensive than in normotensive patients (P < 0.02). Hypertensive patients had significantly higher peripheral resistance than normotensive patients (P < 0.05), while the cardiac index was similar in both groups. Inverse correlations were found between the rate constant for ouabain-sensitive sodium efflux in erythrocytes and both systolic and diastolic pressure (r = −0.43 and r = −0.45, respectively; P < 0.01) and total peripheral resistance (r = −0.76; P < 0.0001). Our data suggest that reduced sodium transport by the Na-K pump plays a role in the pathogenesis of arterial hypertension in patients with chronic uraemia.

Erythrocyte Na,Li Countertransport and Arterial Pressure in Diabetic Adolescents

ABSTRACT. The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty‐nine adolescents with IDDM (17 males, 12 females, mean age 15 ± 0.6 years, mean diabetes duration 11.4 ± 0.7 years) and fifteen healthy age‐matched control subjects (8 males, 7 females, age 14.5 ± 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259‐340) vs. 193 (169‐252) μmol/l RBC/h; p<0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter+). Both systolic and diastolic arterial pressures were significantly higher in Counter+ than in Counter‐ patients. No significant differences were found as regards age, body mass index, diabetes duration, HbAlc, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with In Na,Li countertransport (r=0.38; p<0.05), In [Nai] (r=0.38; p<0.05), and In body mass index (r=0.5; p<0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

Red blood cell Na+, K+ pump activity in patients on hemofiltration

The intracellular concentration of Na+ ([Na+i]) and the Na+ efflux mediated by the Na+, K+ pump were evaluated in red blood cells from 9 patients on hemofiltration, 8 on hemodialysis, 9 on continuous ambulatory peritoneal dialysis (CAPD) and 12 normal subjects. [Na+i] was elevated in CAPD patients only. The rate constant for pump-mediated sodium efflux was close to normal in hemofiltration patients, and significantly reduced in hemodialysis (p +, K+ pump activity of normal red blood cells. Among our uremic patients those on hemofiltration showed a red blood cell Na+, K+ pump activity close to that of normal subjects, possibly related to the absence in their plasma of a circulating pump inhibitor, that seems invariably present in plasma from hemodialysis and CAPD patients.

Selected Abstracts from the 35th Vicenza Course onAKI & CRRT, Vicenza, June 13-16, 2017: Abstracts

Purpose We analyzed the relationship between a positive fluid balance and its persistence over time on acute kidney injury (AKI) development, severity and resolution among ST elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock. Methods We retrospectively studied the cumulative fluid balance intake and output at 96 h following hospital admission in 84 consecutive adult patients with STEMI complicated by cardiogenic shock. The cohort was stratified into two groups, based on the presence or absence of positive fluid balance on day 4. Patients’ records were assessed for the development of AKI, AKI severity and recovery. Results Patients having positive fluid balance were more likely to develop a more severe AKI stage (52% vs. 13%; p < 0.001), were less likely to have recovery of their renal function (29% vs. 75%, p = 0.001), and demonstrated positive correlation between the amount of fluid accumulated and the rise in serum creatinine (R = 0.42, p = 0.004). For every 1 l increase in positive fluid balance, the adjusted possibility for recovery of renal function decreased by 21% (OR = 0.796, 95% CI 0.67–0.93; p = 0.006). Conclusions A positive fluid balance was strongly associated with higher stage AKI and lower rate of AKI recovery in STEMI complicated by cardiogenic shock. Graphical abstract Figure. No Caption available. HighlightsPatients having positive fluid balance were more likely to develop a more severe renal injury.Patients having positive fluid balance were less likely to have recovery of their renal function.Positive correlation between the amount of fluid accumulated and the rise in serum creatinine

Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy

Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=471917.

Effects of canrenone on Na+,K+ ATPase activity, arterial pressure and plasma potassium concentration in uremic hemodialyzed patients.

Canrenone is the main active metabolite1 of the diuretic and antihypertensive drugs spironolactone and canrenoate-K, and competes with aldosterone for a common cytosolic receptor in distal and collecting tubules of the nephron.2 In addition it has recently been demonstrated that canrenone in vitro may directly interfere with ouabain-sensitive Na+,K+ pump (Na+,K+ adenosine triphosphatase), acting as a partial agonist at the digitalis receptor site. 3,4 Moreover Garay et al.4 showed that canrenone is able to restimulate in vitro the Na+,K+ pump of human red blood cells (RBC) blocked by high concentrations of ouabain.