Acid-base abnormalities and liver dysfunction.

In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.

Pathophysiology of Drug-Induced Hypomagnesaemia.

Magnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases)-stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis-make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal excretion of Mg2+. This review presents the function of Mg2+, how it is handled in the kidney and the drugs that cause hypomagnesaemia. The frequency and the number of drugs like diuretics and proton-pump inhibitors (PPIs) that are used daily in medical practice are discussed in order to prevent and treat adverse effects by providing an insight into Mg2+ homeostasis.

The Effect of Dialysis Modality and Membrane Performance on Native Immunity in Dialysis Patients.

Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods. Sixty patients were included in the study and divided in three groups of 20 patients each. Patients on conventional hemodialysis using Low Flux membrane (cHD-LF) were included in Group I, patients on conventional dialysis using High Flux membrane (cHD-HF) were included in Group II and patients treated by on-line hemodiafiltration with High Flux polysulphone membrane (on-line HDF) were included in Group III. Native immunity was investigated using the number of NK-cells and the phagocytic activity of neutrophils. NK-cells count was significantly lower (p<0.001) in the three groups of dialyzed patients in comparison to healthy subjects. However, no significant difference was observed in the NK-cells count among patients treated by conventional dialysis using Low or High Flux membrane and patients treated by on-line hemodiafiltration. Similarly, although the phagocytic activity of neutrophils was significantly decreased in all patients on dialysis (p<0.001), no difference related to the dialysis modality or membrane performance was observed. A strong positive correlation was recognized between parathormone blood levels and number of NK-cells (r=0.305, p<0.01). In conclusion, an impairment of the native immunity represented by NK cell number and phagocytic activity of neutrophils is observed in patients on dialysis. Dialysis modality and membrane performance do not influence the native immunity of dialyzed patients. However, parathormone blood levels are possibly involved in the development of immune system disturbances in such patients.

Estimation of Residual Peritoneal Volume Using Technetium-99m Sulfur Colloid Scintigraphy.

Residual peritoneal volume (RPV) may contribute in the development of ultrafiltration failure in patients with normal transcapillary ultrafiltration. The aim of this study was to estimate the RPV using intraperitoneal technetium-99m Sulfur Colloid (Tc). Twenty patients on peritoneal dialysis were studied. RPV was estimated by: 1) intraperitoneal instillation of Tc (RPV-Tc) and 2) classic Twardowski calculations using endogenous solutes, such as urea (RPV-u), creatinine (RPV-cr), and albumin (RPV-alb). Each method's reproducibility was assessed in a subgroup of patients in two consecutive measurements 48 h apart. Both methods displayed reproducibility (r = 0.93, p = 0.001 for RPVTc and r = 0.90, p = 0.001 for RPV-alb) between days 1 and 2, respectively. We found a statistically significant difference between RPV-Tc and RPV-cr measurements (347.3 ± 116.7 vs. 450.0 ± 67.8 ml; p =0.001) and RPV-u (515.5 ± 49.4 ml; p < 0.001), but not with RPV-alb (400.1 ± 88.2 ml; p = 0.308). A good correlation was observed only between RPV-Tc and RPV-alb (p < 0.001). The Tc method can estimate the RPV as efficiently as the high molecular weight endogenous solute measurement method. It can also provide an imaging estimate of the intraperitoneal distribution of RPV.

Non-secreting benign glucagonoma diagnosed incidentally in a patient with refractory thrombocytopenic thrombotic purpura: report of a case.

Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder, which may be idiopathic or secondary to a variety of diseases. However, there are very few reports of TTP in the context of pancreatic neoplasms. We report a case of relapsing TTP after initial treatment with plasmapheresis, corticosteroids, and rituximab, in a 59-year-old woman. During diagnostic work-up, a pancreatic lesion 35 × 25 mm in size was discovered incidentally and splenopancreatectomy was performed. The pathological diagnosis was benign glucagonoma. The hematological symptoms resolved completely after the procedure and 3 years later, the patient is well with no sign of recurrence of TTP or glucagonoma. To our knowledge, this represents the first documented case of a non-secreting benign pancreatic neuroendocrine tumor (glucagonoma) associated with TTP that is refractory to standard treatment.

Patient clearance time (tp) with different vascular access types.

BACKGROUND/AIMS: The dialysis delivered dose is limited by the rate at which urea can be transferred from the different body compartments. The time needed to clear the peripheral compartments of the body has been called the patient clearance time (tp). The aim of the study was to compare delivered dialysis dose using the tp index between patients dialyzed through a permanent central venous catheter (CVC) and patients with an arteriovenous fistula (AVF). METHODS: The study included 48 stable hemodialyzed patients. Patients were classified into two groups according to their vascular access type. The first group included 24 patients dialyzed through a permanent CVC and the second group consisted of 24 patients with a mature AVF. The following parameters were calculated twice for each patient: tp, Kt/V adjusted for the tp. RESULTS: tp was lower in the AVF dialysis modality than in CVC (26 ± 7 vs. 42 ± 14 min, p<0.001) while the (eqKt/V)tp was higher in AVF than in CVC dialysis (1.36 ± 0.11 vs. 1.19 ± 0.13, p<0.001). CONCLUSIONS: The patient clearance time is lower in AVF than in CVC dialysis, and this is accompanied by a higher delivered dialysis dose.

The impact of hemodialysis on the dispersion of ventricular repolarization.

BACKGROUND: Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias. METHODS: We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio. RESULTS: The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions. CONCLUSIONS: HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated.

Inorganic phosphorus homeostasis during the first hour of dialysis.

BACKGROUND/AIM: Hyperphosphatemia is a well-recognized complication of chronic kidney disease, and phosphorus kinetics during hemodialysis (HD) remains a vague area of investigation. We studied the inorganic phosphorus homeostasis during the first hour of an HD session. MATERIALS/METHODS: Twelve patients were studied twice, in two consecutive HD sessions. Total (TPR), extracellular (EPR), and intracellular (IPR) phosphorus mass removal was determined using the direct dialysate quantification (DDQ) method. Alterations of serum inorganic phosphorus (sP), erythrocyte intracellular phosphorus (P(ERY)), and 2,3-diphosphoglycerate (2,3-DPG) concentrations were measured before HD initiation and at 1, 2, 3, 4, 5, 10, 30, and 60 min. RESULTS: The contribution of IPR to TPR was negative in the first 10 min of both HD sessions (-27.2 ± 6.5 and -26.4 ± 58 mmol, respectively, p = ns) while the contribution of the IPR to TPR increased as the time elapsed. Intracellular phosphorus and 2,3-DPG remained almost unchanged during the 60 min of HD session. CONCLUSIONS: Unchanged P(ERY) concentration during the first hour of an HD session does not reject the hypothesis of a simultaneous efflux and influx of phosphorus from/to intracellular compartment.

Switch from conventional to every other day hemodialysis: a comparison pilot study.

Fluid and solute fluctuations during the week are the main drawbacks of conventional hemodialysis (cHD) in patients' outcomes. The aim of our study was to evaluate the influence of every other day hemodialysis (eodHD) on clinical and laboratory parameters and to compare to that of cHD. Eighteen patients on cHD were included in the study. Nine patients (group I) were randomly switched to eodHD, while the rest (group II) remained on their regular cHD. By the end of the study (12 months) we observed a reduction in body weight followed by a parallel reduction in predialysis mean blood pressure by 7 mm Hg in group I (p<0.05) and the number of antihypertensives. Moreover, a reduction in left ventricular mass and an increment of ejection fraction was observed in group I. Hemoglobin levels remained stable in both groups, but erythropoietin dose was reduced in eodHD group. Dialysis delivered dose (dpKt/V) was higher and urea rebound phenomenon was less in group I. Finally, an improvement in uremia related and postdialysis symptoms was observed in the same group of patients. Our results showed that eodHD improved patients' clinical and biochemical status and therefore might have advantages in patients' outcomes compared with cHD.

Correction of anemia with erythropoietin in chronic kidney disease (stage 3 or 4): effects on cardiac performance.

BACKGROUND: It is not clear whether the correction of anemia with erythropoietin (rhuEpo) in patients with chronic kidney disease (CKD) has any benefit on cardiac function and geometry. Most studies are based on indices of systolic function and left ventricular mass (LVM) and the results are conflicting. PATIENTS AND METHODS: We sought to investigate the effect of rhuEpo on LV systolic and diastolic performance using conventional and novel echocardiographic indices. Thirty one patients with CKD (stage 3 or 4) were included. Fifteen patients (group I) treated with rhuEpo targeting at Hb >or=13.0 g/dL, while the remaining (group II) were not treated. Clinical and laboratory parameters were recorded at baseline and 1 year later. Ejection fraction (EF) and LVM were carefully determined. Diastolic function was assessed by mitral inflow indices (E and A wave velocities, Edt deceleration time and E/A) and novel indices of mitral annulus motion using Tissue Doppler Imaging (Em, Am, and E/Em). An index of global cardiac function (Tei) was also calculated. RESULTS: At baseline, the 2 groups had comparable clinical and laboratory characteristics. After 1 year, a significant improvement in Hb levels (13.6 +/- 1.2 vs 10.3 +/- 1.2 g/dL, p < 0.05) as well as in systolic and diastolic function indexes was observed in group I compared to group II patients: EF (70.5 +/- 7.6 vs 63.4 +/- 9.3%, p < 0.05), LVM (116.5 +/- 34.9 vs 155.6 +/- 51.6 g/m(2), p < 0.05), Edt (233.9 +/- 98.6 vs 166.9 +/- 45.1 ms, p < 0.05), Tei index (0.35 +/- 0.12 vs 0.51 +/- 0.17, p < 0.01) and E/Em (9.7 +/- 2.4 vs 14.8 +/- 5.2, p < 0.05), respectively. Blood pressure and heart rate did not show significant changes. CONCLUSIONS: Correction of anemia with rhuEpo in patients with CKD seems to improve cardiac performance and geometry.

Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs.

BACKGROUND/AIM: Idiopathic membranous nephropathy, the most common cause of nephrotic syndrome in adults, has been traditionally treated with corticosteroids and cytotoxic drugs. Ciclosporin A (CsA) is used in resistant cases, but also as a first-line treatment, due to the serious side effects of cytotoxic drugs. In this study, the remission rates of nephrotic syndrome and the incidence of side effects of corticosteroids and low CsA doses are compared with those after treatment with cytotoxic drugs. METHODS: Seventy-seven nephrotic patients with well-preserved renal function who were treated with methylprednisolone and CsA (n = 46) or cytotoxic drugs (n = 31) were studied. The effects of treatments were estimated on the basis of remission rates of nephrotic syndrome and preservation of the renal function. RESULTS: Remission (complete or partial) of nephrotic syndrome was observed in 85% of the patients treated with CsA and in 55% of the patients treated with cytotoxic drugs (p < 0.01). Deterioration of the renal function, more common in patients with multiple relapses and interstitial fibrosis, was observed in 26 and 23% of the patients, respectively (p = NS). Serious side effects and discontinuation of treatment were more frequent in patients treated with cytotoxic drugs (10 vs. 4%). CONCLUSION: The combination of corticosteroids with CsA represents a better regimen for patients having idiopathic membranous nephropathy, since it is associated with higher remission rates of nephrotic syndrome and less severe side effects than corticosteroids and cytotoxic drugs.

Acute effect of heparin on lipid parameters in patients on renal replacement therapy.

Dialyzer membrane and the type of heparin used can influence lipid parameters. However, there are limited and debatable data concerning lipid alterations during a single hemodialysis session. Moreover, the role of hemoconcentration after every hemodialysis session confuses the real effect of the heparin on lipid profile. We investigated the acute effect of heparin administration on lipids in hemodialysis patients, but on an off-hemodialysis day in order to eliminate any effect of ultrafiltration. We studied six patients on hemodialysis, six patients on peritoneal dialysis, and six healthy persons. The study was performed in two phases (1 week apart). In phase A, we used unfractionated heparin (5000 IU, intravenous), whereas in phase B, low-molecular-weight heparin (3500 anti-FXa, intravenous) was used. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and Lp(a) were estimated before and 1, 2, 3, and 4 hours after heparin administration. We observed a reduction only in triglycerides (at the first, second, and third hour) in both phases in all groups. The other lipid parameters were not affected. In conclusion, acute administration of both types of heparin seems to affect only triglyceride levels in patients on renal replacement therapy.

Oxidative stress is progressively enhanced with advancing stages of CKD.

BACKGROUND: Oxidative stress appears to have a central role in the pathophysiological process of uremia and its complications, including cardiovascular disease. However, there is little evidence to suggest how early oxidative stress starts developing during the progression of chronic kidney disease (CKD). The aim of this study is to assess oxidative stress activity in a cross-sectional study of patients with CKD stages 1 to 4. METHODS: Eighty-seven steady patients (47 men, 40 women) with a median age of 62 years (range, 28 to 84 years) and mean estimated glomerular filtration rate (eGFR) of 57 mL/min (0.95 mL/s) were studied. Levels of plasma 8-isoprostanes (8-epiPGF2a) and serum total antioxidant status (TAS) were used as markers of oxidative stress. 8-epiPGF2a levels were determined by using an enzyme-linked immunosorbent assay method, whereas a chromatometric method was used to determine TAS. RESULTS: Plasma 8-epiPGF2a levels increased significantly as CKD stages advanced (P < 0.001). There was a highly significant inverse correlation between 8-epiPGF2a level and GFR (P < 0.01). Serum TAS levels also increased in a similar fashion (P < 0.009) and showed a significant inverse correlation with GFR (P < 0.01). 8-epiPGF2a and TAS levels showed a positive correlation (P < 0.05). Multiple regression analysis showed that the most significant predictor variable for 8-epiPGF2a level was eGFR, whereas the association between eGFR and TAS was affected strongly by confounding variables, mainly uric acid level. CONCLUSION: Oxidative stress appears to increase as CKD progresses and correlates significantly with level of renal function. Increased TAS seems to be dependent on several confounding variables, including increased uric acid levels, and therefore does not seem to be a reliable method for assessing the antioxidant capacity of patients with CKD. These results suggest that larger studies using the correct markers to assess the timing and complex interplay of oxidative stress and other risk factors during the progression of CKD should be carried out.

Long-term treatment with EPO increases serum levels of high-density lipoprotein in patients with CKD.

BACKGROUND: Among lipid abnormalities observed in patients with chronic kidney disease (CKD) is a significant decrease in serum high-density lipoprotein cholesterol (HDL-C) levels. In a previously published randomized control trial, we showed that early erythropoietin (EPO) administration in a predialysis population slowed the progression of CKD. In the present nested substudy, we examine whether EPO has an influence on serum HDL-C levels in comparison to other lipid parameters in this population. METHODS: Eighty-eight patients with CKD stages 3 and 4 were enrolled in the study. Forty-five patients (group 1) were treated with EPO (50 U/kg/wk), targeting to increase hemoglobin levels to 13 g/dL or greater (>or=130 g/L). The other patients (group 2) remained without treatment until hemoglobin levels decreased to less than 9 g/dL (<90 g/L). The duration of the study was 12 months. RESULTS: At the end of the study, we observed a statistically significant decrease in serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides in both groups. However, serum HDL-C levels significantly increased in only group 1 (from 42.5 +/- 10.4 to 55.9 +/- 8.1 mg/dL [1.10 +/- 0.27 to 1.45 +/- 0.21 mmol/L]; P < 0.001), whereas they were unchanged in group 2. In addition, a significant decrease in atherogenic LDL-C/HDL-C ratio was observed in only group 1. Importantly, the increase in serum HDL-C levels correlated positively with the increase in hemoglobin values in EPO-treated patients. CONCLUSION: Our results show that EPO treatment of predialysis patients with CKD significantly increases serum HDL-C levels, which may represent an important antiatherogenic effect of this hormone.

Sevelamer hydrochloride versus aluminum hydroxide: effect on serum phosphorus and lipids in CAPD patients.

BACKGROUND: Dietary phosphorus restriction, oral administration of phosphorus binders, and dialysis are the main strategies to control hyperphosphatemia in patients with stage 5 chronic kidney disease. Aluminum hydroxide (AH) and calcium carbonate, the most commonly used phosphorus binders, have serious disadvantages, such as aluminum toxicity and hypercalcemia. Sevelamer hydrochloride (SH) is a relatively new nonabsorbed calcium- and aluminum-free phosphorus binder. The present study was designed to evaluate the efficacy of SH in the control of hyperphosphatemia and its effect, compared to AH, on serum lipid parameters in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: 30 stable patients on CAPD were included in an open-label, randomized crossover study. After a 2-week phosphorus binder washout period, 15 patients (group I) were administered SH for 8 weeks and in the remaining patients (group II), AH was introduced (phase A). After a new 2-week washout period, patients crossed over to the alternate agent for another 8 weeks (phase B). RESULTS: There were similar reductions in serum phosphorus levels over the course of the study with both agents: by 1.18 +/- 0.07 mg/dL (0.38 +/- 0.03 mmol/L) with SH and by 1.25 +/- 0.15 mg/dL (0.40 +/- 0.05 mmol/L) with AH in phase A (p = NS), and by 1.35 +/- 0.25 mg/dL (0.43 +/- 0.08 mmol/L) with AH and by 1.23 +/- 0.80 mg/dL (0.39 +/- 0.25 mmol/L) with SH in phase B (p = NS). Moreover, SH administration was associated with a 10.5% +/- 9.4% and a 20.1% +/- 6.8% fall in total cholesterol (p < 0.05) and low-density Lipoprotein cholesterol (p < 0.001) in phase A, and 11.9% +/- 7.2% (p < 0.05) and 21.5% +/- 2.4% (p < 0.001), respectively, in phase B. In both phases of the study, AH administration was not followed by a significant change in serum lipid parameters. CONCLUSION: Sevelamer hydrochloride is a well-tolerated alternative to calcium- or aluminum-containing phosphorus binder in the control of serum phosphorus in CAPD patients. Furthermore, SH improves the lipid profile in these patients.

Role of the dialyzer membrane on the overall phosphate kinetics during hemodialysis.

BACKGROUND/AIM: We investigated the potential role of the membrane type on phosphate kinetics. METHODS: Six patients on dialysis (HD) were studied using modified cellulose (Hemophan), ethylene-vinyl alcohol (EVAL) and polyacrylonitrile (PAN). Total (TPR), extracellular (EPR) and intracellular (IPR) phosphate removal and effective dialyzer phosphate clearance (K(d)) were determined by the DDQ method. The intercompartment transfer coefficient (K(C)) was calculated using a mathematical model. Erythrocyte phosphate (P(ERY)) and 2,3-biphosphoglycerate (2,3-BPG) concentrations were determined before and after HD. RESULTS: TPR was 1.2+/-0.4, 1.10+/-0.4 and 1.09+/-0.4 g with Hemophan, EVAL and PAN, respectively (p=n.s.). EPR and IPR were independent of membrane type. There was no difference in K(C) between membranes (321+/-70, 338+/-92 and 341+/-83 ml/min, respectively). The P(ERY) and 2,3--BPG remained statistically insignificant for all membranes. CONCLUSION: Our results show that the type of membrane does not influence the kinetics of phosphate during dialysis, neither in the transfer from plasma to dialysate nor from the intra- to the extracellular compartment.

Phantom cytomegalovirus infection in vasculitis patients: what it means and what to do.

We report our experience and hypothesis on the diagnosis and treatment of patients with vasculitis who are simultaneously diagnosed with serum-positive cytomegalovirus (CMV) immunoglobulin (Ig)M antibodies and negative CMV DNA polymerase chain reaction (PCR). It remains unknown how to treat this kind of "phantom" CMV infection. In a patient diagnosed with Henoch-Schönlein vasculitis, CMV IgM titers were increased while angiitis and renal function deteriorated. Empiric treatment of phantom CMV infection with ganciclovir in this CMV IgM-positive and PCR-negative patient resulted in complete vasculitis remission, serum CMV antibody seroconversion, and renal function improvement. These results imply something more than coincidence.

Influence of the type of membrane and heparin on serum lipid parameters during a dialysis session: a pilot study.

BACKGROUND/AIM: The type of heparin and membrane used might influence the lipids in patients on hemodialysis (HD). However, there are limited and debatable data concerning the lipid changes during an HD session. The aim of our study was to examine the changes in serum lipid parameters during the HD session in relation to the heparin and dialysis membrane used. METHODS: Ten patients on HD 3 times/week participated in the study. The study was performed in three phases (A, B, C), each of 1 week's duration. The types of membranes used were Hemophan (phase A), ethylene vinyl alcohol (phase B) and polyacrylonitrile (phase C), respectively, in a random order. During the midweek session of each phase we used classic heparin, while during the session at the end of the week low molecular weight heparin was administered. Serum total cholesterol, triglycerides, HDL cholesterol, Lp(a), albumin and total proteins were measured before and 5 min after the HD and hourly during the HD session. RESULTS: In all phases, we found a progressive increase in all lipid parameters during the HD session, except Lp(a). This increase, however, was possibly due to hemoconcentration. CONCLUSIONS: This pilot study showed that (1) the type of heparin and membrane used does not seem to affect the serum lipid profile during a single HD procedure, and (2) the changes observed in serum lipid parameters are mainly due to hemoconcentration.