Potassium metabolism in continuous ambulatory peritoneal dialysis patients

Background: Hypokalemia is common and may have contributed to the poor clinical outcome in peritoneal dialysis (PD) patients. In this study, we made a detailed investigation on the potassium metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients and tried to find out the possible factors associated with the high prevalence of hypokalemia in PD patients. Methods: A cross-sectional survey in 243 clinically stable CAPD patients was made in our PD center in 2010. Patients were divided into four groups according to whether they were anuric or not and different dialysis regimens. Patients’ demographic data and data on potassium metabolism including dietary potassium intakes, residual renal potassium, and peritoneal dialysis potassium removal were collected. Results: The average potassium intake in our 243 PD patients was 32.1?±?11.1?mmol/day. The total potassium removal was significantly higher in non-anuric patients as compared to anuric patients (33.2?±?9.1 vs. 23.0?±?4.7?mmol/day for 3 exchanges per day and 35.2?±?8.9 vs. 28.6?±?6.3?mmol/day for 4 exchanges per day, respectively, p?p?p?p?R² linear?=?0.645, p?Conclusions: Our study suggested that if potassium intake was limited in PD patients, we should be aware of the risk of hypokalemia with high doses of PD when patients have good RRF. Our study also suggested that potassium removal in PD patients may not necessarily reflect potassium intake even if serum potassium is normal, the effect of ICW should be considered when evaluating potassium homeostasis.     

Hyporesponsiveness to Erythropoietin Therapy in Hemodialyzed Patients: Potential Role of Prohepcidin,Hepcidin, and Inflammation

Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFα and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFα, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy.     

The Red Blood Cell Deformability in Patients Suffering from End Stage Renal Failure on Hemodialysis or Continuous Ambulatory Peritoneal Dialysis

Anemia is the main problem for patients suffering from end stage renal disease (ESRD). This study aimed to determine whether the index of rigidity (IR), that shows red blood cells (RBCs) deformability and the possible IR disturbances can provide an explanation about the cause of anemia, in patients undergoing maintenance hemodialysis (HD) or on peritoneal dialysis. The IR was determined in 39 hemodialyzed patients, who were already in dialysis for a period of time ranging from 16 to 120 months (mean ± SD = 41.8 ± 24.1) (Group A). Furthermore, the IR was measured in 32 patients on continuous ambulatory peritoneal dialysis (CAPD), who were in CAPD for a period of time ranging from 6 to 60 months (mean ± SD = 10.7 ± 9.9) (Group B). Finally, the IR was determined in 17 normal individuals (group C). The RBCs IR was measured twice in group A (before and after the end of a hemodialysis session) and once in groups B and C. The IR was determined by hemorrheometry (method of filtration), using special equipment. In group A the IR was increased in comparison to the control group (C) (17.9 ± 6.2 vs. 10.2 ± 1.8, p < 0.0001). This increase was even higher in the measurement at the end of the hemodialysis session (paired t‐test, p < 0.0001). The RBCs IR in CAPD patients was significantly lower than that of HD patients (12 ± 3.8 vs. 17.9 ± 6.2, p < 0.0001) and was not statistically different from the control group (12 ± 3.8 vs. 10.2 ± 1.8, p = 0.068). It is concluded from the study that: 1) in HD patients occur disturbances in the deformability of the RBCs, that are worsened by the hemodialysis session; 2) the index of rigidity of RBCs is significantly higher in the HD patients than in CAPD patients; 3) in patients on CAPD, the disturbance of deformability of the RBCs was less in comparison to the control group, which however does not reach the statistically significant levels.     

Heart Rate Variability,Left Ventricular Functions,and Cardiac Autonomic Neuropathy in Patients Undergoing Chronic Hemodialysis

Objective.?Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). Methods.?Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P₁ and P₂) and the central frequencies (F₁ and F₂) of low and of high frequency spectral bands were recorded. Results.?End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 ± 21.1 mL vs. 34.0 ± 14.3 mL and 131.5 ± 37.3 mL vs. 96.9 ± 18.9 mL, p<0.01, p<0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 ± 2.4% vs. 63.7 ± 10.1% and 0.29 ± 0.01 vs. 0.34 ± 0.07, p<0.001, p<0.05, respectively). P1 and P2 were decreased in Group II than in Group I (136.2 ± 173.9 m s² vs. 911.0 ± 685.5 and 96.5 ± 149.6 vs. 499.7 ± 679.5, p<0.001, p<0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p<0.01, r = 0.68 p<0.001, r = 0.65 p<0.002, r = 0.66 p<0.02, and r = 0.69 p<0.01). Conclusion.?As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.     

Gastric Emptying in Patients on Renal Replacement Therapy

In addition to gastrointestinal tract symptoms such as nausea, vomiting, and loss of appetite, impaired gastric emptying time (GET) may be related to nutritional parameters and nutritional status of patients on renal replacement therapy (RRT). Patients on RRT are affected by several factors such as uremic toxins, the presence of dialysate in the peritoneal cavity, and the drugs used against renal allograft rejection. In this study, we investigated the gastric emptying time and its relationship with biochemical and nutritional parameters in patients on RRT: those on hemodialysis and peritoneal dialysis, and renal transplantation patients. Seventy‐five patients, 44 on hemodialysis, 16 on peritoneal dialysis, and 15 renal transplant patients, were included in the study. They were examined for gastric emptying time using a radioisotopic method. The results were compared with the GET of healthy subjects. Each group of patients was evaluated in terms of hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, blood glucose, total protein, albumin, serum lipids, parathyroid hormone (PTH) and body mass index and biceps and triceps skinfold. The mean GET of patients on RRT was significantly longer than the mean GET of healthy subjects (87.8 ± 23.4 vs. 55 ± 18 min, p < 0.05). The mean GET of each therapy subgroups was significantly longer than the healthy subjects (the mean GET was 85.1 ± 22.4 min for hemodialysis, 87.7 ± 31.8 min for peritoneal dialysis, and 94.6 ± 16.7 min for renal transplant patients, respectively, p < 0.05). On the other hand, the differences in the mean GET between the three therapy subgroups were not statistically significant (p > 0.05). In addition, time on replacement therapy inversely and blood glucose positively correlated with GET in renal transplant patients. In conclusion, GET was longer in patients on all three RRT modalities than in healthy subjects. GET was not significantly different in dialysis patients and renal transplant patients.     

INSULIN AND MINERALOCORTICOIDS INFLUENCE ON EXTRARENAL POTASSIUM METABOLISM IN CHRONIC HEMODIALYSIS PATIENTS

Insulin-mineral corticoids effects on extrarenal K⁺ metabolism in dialysis patients. During the inter-dialytic interval in dialyzed patients, hydrogen and potassium ions are regulated by extrarenal mechanisms. We studied the hormonal and acidotic effects on the extrarenal potassium metabolism, in selected, anuric and stable, hemodialysis patients. Fifteen patients, were grouped according to the mean mid-week pre-dialysis K⁺ over the past 12 months: > 6.0 mEq/L (G1, n = 5), = 5.1–6.0 mEq/L (G2, n = 5), ≤5.0 mEq/L (G3, n = 5). After a mid-week hemodialysis session and 12 h fasting, they received 1 g/Kg glucose p.os (A). Insulin, aldosterone, renin, pH, HCO₃^?, glucose, body weight, blood pressure and heart rate were measured before and 60′ after the meal. We recorded the same parameters, except insulin, in 15 patients, similarly grouped, before hemodialysis (T0) and on 3 consecutive off dialysis days (T1–T3); G1 received fluorohydrocortisone (FHC) 0.1 mg–0.3 mg/day, according to body weight and G3 spironolactone (SLT) 200 mg per day. G2 were controls (B). (A) A significant rise in glycemia (81 ± 23 to 157 ± 52 mg/dL, P < 0.001) and insulin (11.8 ± 6.2 to 46.8 ± 19.5 μU/mL, P<0.001), with a drop in K⁺ (5.1 ± 0.6 to 4.8 ± 0.7 mEq/L, P= 0.001) and aldosterone (453 ± 373 to 383 ± 364 pg/mL, P<0.01), were noted at T60 vs. T0, in all groups. Insulin levels correlated negatively (r = ?0.54, P<0.04) to serum K⁺ at T60, in all patients. (B) No major pH, HCO₃ and aldosterone changes were observed in the 3 groups. Despite that, K⁺ dropped in G1 by FHC (6.7 ± 0.9 to 5.9 ± 0.6 mEq/L, P<0.05), rose in G3 by SLT (4.4 ± 0.4 to 5.4 ± 0.3 mEq/L, P<0.05) and remained unchanged in controls (5.8 ± 0.2 to 5.8 ± 0.6 mEq/L), (T0 vs T3 pre-dialysis values). Glucose significantly lowered K^? by promoting adequate insulin secretion. Drugs affecting aldosterone action significantly influenced potassium metabolism. Acid-base balance was not important in K⁺ handling in steady state anuric dialysis patients.     

Beneficial Effect of Intrarenal Verapamil in Human Acute Renal Failure

Cellular Ca²⁺ influx during the reperfusion period after an ischemic insult has been proposed to be a crucial pathogenetic factor in the development of experimental acute renal failure (ARF). The present study, therefore, examined the potential beneficial effect of intrarenal verapamil, a calcium entry blocking agent, on ARF in patients. Twelve patients were enrolled in the study. Six ARF patients (experimental group)—ARF caused by malaria (4 patients) and leptospirosis (2 patients)—had a catheter placed in their renal artery; verapamil was infused at 100 μg/minfor 3 h and intravenous furosemide, 0.8 mg/kg/h x 24 h was also administered. Another six ARF patients (control group)—ARF caused by malaria (5 patients) and leptospirosis (1 patient)—were treated with intravenous furosemide alone. Baseline renal function was comparable in both groups; GFR (3.16 ± 3.24 vs 0.7 ± 1.5 mL/min, NS), serum creatinine (S_cr), (9.1 ± 2.1 vs 11.3 ± 2.2 mg/dL, NS), and urine volume (V) (41.79 ± 4.77vs 34.54 ± 13.52 mL/h, NS), were comparable in the experimental and control groups. Twenty-four hours posttreatment, the increment of GFR (9.66 ±4.25 vs 1.32 ± 0.50mL/min, P <. 02) and V (181.8 ± 61.7vs 79 ± 18mL/h, P <. 04), were significantly greater in the experimental group as compared to the control group. The course of ARF was also shorter in the experimental group (6.5 ±2.1 vs 13 ± 1.1 days, P <. 05), who also required less dialysis. Thus, combination of a renal arterial infusion of verapamil and intravenous furosemide significantly improves the renal function in tropical ARF as compared to intravenous furosemide alone.     

Placental Growth Factor in Patients with Decreased Renal Function

Background: Patients with decreased renal function are characterized by high cardiovascular morbidity and mortality due to complications of premature atherosclerosis. Placental growth factor (PlGF) is a proatherogenic cytokine and new biomarker of cardiovascular events. The aim of this study was to determine PlGF levels and describe their relationship to renal function and risk factors of atherogenesis in patients with decreased renal function. Methods: The study group consisted of 114 subjects: 45 patients with various degrees of decreased renal function (CHRI), 31 long-term hemodialysis (HD) patients, and 38 age-matched healthy control subjects. PlGF was assessed immunochemically (enzyme-linked immunosorbent assay) and routine biochemical parameters were measured using standard laboratory methods. Results: PlGF levels were significantly increased in CHRI and HD patients compared to controls (10.5 ± 3.3 pg/mL in CHRI patients and 11.5 ± 3.4 pg/mL HD patients vs. 8.1 ± 1.8 pg/mL in controls, both p < 0.0001). In CHRI patients, PlGF was detectable in the urine, and its urine concentration correlated with its serum levels. In HD patients, PlGF correlated with low-density lipoproteins (r?=?0.36, p < 0.05), but was not related to C-reactive protein levels. Higher levels of PlGF were found in CHRI patients with cardiovascular disease, compared with those free of such complication. Conclusions: PlGF levels are increased in patients with decreased kidney function. PlGF is detectable in the urine, and serum and urine levels of PlGF are significantly interrelated. It is higher in CHRI patients with cardiovascular disease. Further studies are required to demonstrate the usefulness and significance of PlGF in patients with chronic kidney disease.     

Serum Level of Soluble Fibrinogen-Like Protein 2 in Renal Allograft Recipients With Acute Rejection: A Preliminary Study

BackgroundSoluble fibrinogen-like protein 2 (sfgl2), which is mainly secreted by T cells, is a novel effector of regulatory T cells with immunosuppressive functions. The aim of this study was to investigate serum levels of sfgl2 among renal allograft recipients.MethodsFrom November 2010 to August 2011 we retrospectively divided 47 renal allograft recipients into an acute rejection (n = 19) versus a stable group (n = 28) according to allograft biopsy results, using the Banff 2007 classification. The acute rejection group was subdivided into grade I (n = 8) versus grade II T-cell–mediated (n = 6) or antibody-mediated rejection episodes (n = 5). Peripheral blood samples were collected at the time of biopsy. Fourteen healthy volunteers were included as normal group controls. Serum levels of sfgl2 were analyzed by enzyme-linked immunosorbent assay.ResultsSerum levels of sfgl2 were increased among renal allograft recipients suffering from biopsy-proven acute rejection episodes (61.91 ± 45.68 ng/mL), versus those with stable allografts (38.59 ± 19.92 ng/mL, P < .05) or healthy volunteers (29.10 ± 18.08 ng/mL, P < .05). The sfgl2 level was significantly higher among patients with antibody-mediated (118.48 ± 55.54 ng/mL) than T-cell–mediated acute rejection episodes (41.71 ± 16.44 ng/mL, P < .01). Serum sfgl2 levels were remarkably elevated in patients with grade II (51.87 ± 19.13 ng/mL) versus grade I T-cell–mediated rejection (34.10 ± 9.26 ng/mL, P < .05).ConclusionsSerum sfgl2 levels were increased among renal allograft recipients with acute rejection episodes to an extent dependent upon the pathological type and severity of the response.     

High serum chemerin level in CKD patients is related to kidney function,but not to its adipose tissue overproduction

Abstract

Chemerin is an adipokine modulating inflammatory response and affecting glucose and lipid metabolism. These disturbances are common in CKD. The aim of the study was: (a) to evaluate circulating chemerin level at different stages of CKD; (b) to measure subcutaneous adipose tissue chemerin gene expression; (c) to estimate the efficiency of renal replacement therapy in serum chemerin removal. 187 patients were included into the study: a) 58 patients with CKD; (b) 29 patients on hemodialysis; (c) 20 patients after kidney transplantation. 80 subjects constituted control group. Serum chemerin concentration was estimated by ELISA. The adipose tissue chemerin mRNA level was measured by RT-qPCR. The mean serum chemerin concentration in CKD patients was 70% higher than in the control group (122.9?±?33.7 vs. 72.6?±?20.7?ng/mL; p?<?0.001) and it negatively correlated with eGFR (r?=??0.71, p?<?0.001). The equally high plasma chemerin level was found in HD patients and a HD session decreased it markedly (115.7?±?17.6 vs. 101.5?±?16.4?ng/mL; p?<?0.001). Only successful kidney transplantation allowed it to get down to the values noted in controls (74.8?±?16.0 vs. 72.6?±?20.7?ng/mL; n.s.). The level of subcutaneous adipose tissue chemerin mRNA in CKD patients was not different than in patients of the control group. The study demonstrates that elevated serum chemerin concentration in CKD patients: (a) is related to kidney function, but not to increased chemerin production by subcutaneous adipose tissue, and (b) it can be efficiently corrected by hemodialysis treatment and normalized by kidney transplantation.     

Pentoxifylline improves haemoglobin and interleukin‐6 levels in chronic kidney disease

Aim: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin‐6 (IL‐6) and improved iron mobilization. Background: CKD patients may have elevated IL‐6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL‐6 expression. Methods: We studied 14 patients with stages 4–5 CKD (glomerular filtration rate <30mL/min per 1.73 m²) due to non‐inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin‐stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run‐in period of 3 weeks and during 4 weeks of pentoxifylline treatment. Results: Ten patients (eGFR 23 ± 6 mL/min) completed the study. At the end of the run‐in period average haemoglobin was 111 ± 5 g/L, ferritin 92 ± 26 µg/L, transferrin saturation 15 ± 3% and circulating IL‐6 10.6 ± 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL‐6 (6.6 ± 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 ± 5%, P < 0.003) and decreased serum ferritin (81 ± 25 µg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 ± 6 g/L by week 4 (P < 0.001). Conclusions: Pentoxifylline reduces circulating IL‐6 and improves haemoglobin in non‐inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin.     

The oxalate level in ultrafiltrate fluid collected from a dialyzer is useful for estimating the plasma oxalate level in hemodialysis patients

Background Patients on chronic hemodialysis are likely to develop secondary hyperoxalemia. It is, however, difficult to measure plasma oxalate levels. To measure plasma oxalate levels, rapid plasma separation, deproteinization, and acidification are essential in preventing the formation of oxalate and the deposition of calcium oxalate within the test tube. The present study was undertaken to examine whether the oxalate level in dialyzer ultrafiltrate is potentially useful for estimating plasma oxalate levels. Methods In nine patients on chronic hemodialysis, the plasma, after deproteinization with a filter, and the ultrafiltrate from the dialyzer before hemodialysis were acidified to a pH level of less than 3, followed by the measurement of oxalate levels by ion chromatography. Also, oxalate levels were compared between acidified and non-acidified ultrafiltrates from the dialyzer. In the second part of the study, seven patients on chronic hemodialysis receiving erythropoietin therapy, in whom the ferritin level was more than 300 ng/ml and transferrin saturation was less than 25%, were intravenously administered ascorbic acid, 100 mg, three times a week, after each dialysis session to facilitate the utilization of stored iron. This treatment was continued until the serum ferritin level decreased to a level below 300 ng/ml (for 3 months, at a maximum). The oxalate level in the dialyzer ultrafiltrate after this treatment was compared with that before treatment. Results The mean ± SE oxalate level in the dialyzer ultrafiltrate was 45 ± 6 μmol/l, essentially equal to the plasma oxalate level (46 ± 7 μmol/l). The plasma oxalate level had a significant positive correlation with the dialyzer ultrafiltrate oxalate level (plasma oxalate level = 0.99 × dialyzer ultrafiltrate oxalate level + 1.5; r = 0.95; P < 0.0001). The oxalate level in the acidified ultrafiltrate (45 ± 6 μmol/l) did not differ significantly from that in the non-acidified ultrafiltrate (45 ± 6 μmol/l). The mean ± SE duration of ascorbic acid administration was 64 ± 13 days. The hemoglobin level remained unchanged at 9.6 ± 0.4 g/dl, whereas the serum iron level increased significantly, from 34 ± 2 μg/dl to 43 ± 4 μg/dl (P < 0.05), and serum ferritin levels decreased significantly, from 645 ± 219 ng/ml to 231 ± 30 ng/ml after the treatment (P < 0.05). The oxalate level in the acidified ultrafiltrate showed no significant change after ascorbic acid administration (31 ± 8 μmol/l vs 47 ± 7 μmol/l). Conclusions In patients on chronic hemodialysis, the oxalate level in acidified ultrafiltrate from the dialyzer was found to be useful for estimating the plasma level of non-protein-bound oxalate. When administering ascorbic acid to hemodialysis patients, the plasma oxalate level can be monitored using this method.     

Renal Function After Cardiac Surgery: Adverse Effect of Furosemide

Renal failure is a frequent event after cardiopulmonary by-pass. Hemodynamic alterations that occur during surgery, as well as factors depending on the host, are the main risk factors for renal dysfunction. To evaluate the frequency and risk factors for renal dysfunction in this setting, a cohort of fifty patients with preoperative serum creatinine under 1.5 mg/dL, submitted to cardiac surgery with cardiopulmonary by-pass was analyzed. Variables related to preoperative patient condition, intraoperative and postoperative periods were recorded. Renal function was assessed by clearances of creatinine, urea and free water, also by fractional excretion of sodium (FENa), at baseline, at anesthetic induction and during postoperative period. Patients were arbitrarily divided in two groups, according to the serum creatinine (S_Cr) value at the end of the postoperative period: Group I: S_Cr <2 mg/dL (n = 44 patients (88.5%)) and Group II: S_Cr >2 mg/dL (n = 6 patients (11.5%)). A decrease of renal function was observed in all patients: creatinemia raised from 1.04 ± 0.2 to 1.55 ± 0.4 mg/dL (33%), associated with a rise in FENa. Differences between group I and group II using univariate analysis were: baseline serum creatinine (1.01 ± 0.23 mg/dL vs. 1.26 ± 0.19 mg/dL, p = 0.03), FENa (0.99 ± 0.8 vs. 2.2 ± 2.1, p = 0.04), furosemide dose during surgery normalized to body surface area (93.2 ± 23 mg/1.73 m² BSA vs. 135 ± 38 mg/1.73 m² BSA, p<0.001), and hemodilution index (17.3 ± 4.3% vs. 22.8 ± 3.2%, p<0.01). In the multiple regression model, baseline creatinemia and furosemide dose were associated to renal dysfunction.     

Plasma levels of endothelin-1 in patients with the hepatorenal syndrome after successful liver transplantation

The hepatorenal syndrome (HRS) is characterized by renal vasoconstriction leading to deterioration of renal function in patients with liver disease. A possible role of endothelin-1 (ET-1) in the pathogenesis of HRS has been suggested, but a correlation between ET-1 plasma levels and the development of HRS as well as the recovery from HRS following OLT has not been shown yet. We performed longitudinal measurements of ET-1 plasma levels in four groups of patients, 5 patients with HRS before and after orthotopic liver transplantation (OLT), 10 patients without HRS undergoing OLT, 20 patients with chronic renal failure but without liver disease, and 12 healthy controls. Before OLT, plasma levels of ET-1 were higher in patients with HRS (19.5 ± 8.6 ng/l, P < 0.001; n = 5) compared to patients without HRS (4.9 ± 1.1 ng/l; n = 10), normals (1.2 ± 0.18 ng/l; n = 12), and patients with chronic renal failure (2.4 ± 0.4 ng/l; n = 20). Patients with HRS compared to patients without HRS had higher levels for creatinine (2.42 ± 0.6 vs. 0.89 ± 0.05 mg/dl, P < 0.05), creatinine clearance (107 ± 9 ml/min vs. 44.6 ± 5.5 ml/min, P < 0.001), and bilirubin (11.4 ± 3.8 vs. 3.7 ± 1 mg/dl, P < 0.05) before OLT. Within one week after OLT, there was a rapid decrease in ET-1 levels in patients with HRS while creatinine and bilirubin levels decreased slower. Regression analysis revealed a weak correlation between serum creatinine and ET-1 (r = 0.192, P = 0.04) and a significant correlation between serum bilirubin and ET-1 (r = 0.395, P < 0.001). The means of the ET-1 levels decreases rapidly with improvement of liver function after OLT. Levels of ET-1 correlate with excretory liver function assessed by bilirubin. The fall in ET-1 levels preceding improvement of renal function further strengthens the concept of ET-1 being a causative factor in HRS. Received: 22 July 1999/Revised: 28 January 2000/Accepted: 11 May 2000     

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

Background: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.

Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.

Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64?±?3.6 and 70?±?5.3?ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36?±?2.5; pHMGB1:30.5?±?7.0?ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5?±?7.0 versus 6.9?±?3.6; p?p?=?0.01). An inverse correlation was found between TGF-β levels and dialysate/plasmatic creatinine values (r = ?0.83; p?=?0.03).

Conclusion: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-β could predict the peritoneal transport status and dialysis technique adequacy.     

Renal function in the oldest-old on an acute geriatric ward

Aim: Evaluation of renal function and relation to risk factors for renal failure in very old patients admitted to an acute geriatric ward. Methods: Retrospective chart review ofpatients aged 80 years and over, admitted to the acute geriatric ward from August 1998 till August 1999. Recorded data were: age,gender, previous medical history, primary diagnosis, medicationuse, weight, serum creatinine, BUN, sodium, potassium,cholesterol, urine and ultrasound of the kidney. The creatinine clearance was estimated by the Cockcroft-Gault formula, the glomerular filtration rate by the MDRD equation. Results: 220 (60males/160 females) patients were included. The mean serum creatinine on admisssion and discharge was 1.17 ± 0.45 mg/dL and1.11 ± 0.48 mg/dL respectively. The mean estimated creatinine clearance in the very old was 38.11 ± 12.04 mL/min on admissionand 39.00 ± 11.01 mL/min on discharge. Renal failure arbitrarily defined as an estimated creatinine clearance on admission of less than 30 mL/min was found in 26.4% of the patients. Only a significant correlation between failure to thrive and renal failure was found (p < 0.0001). The correlation coefficient between the Cockcroft-Gault and the MDRD formula was r = 0.66 (p < 0.0001);between the Cockcroft-Gault and the reciprocal serum creatinine wasr = 0.60 (p < 0.0001) and between the MDRD and the reciprocal serum creatinine was r = 0.87 (p < 0.0001). Conclusion: The weak correlation between the Cockcroft-Gault and other estimations ofGFR in the acutely ill elderly, confirms the need to have areliable estimation of glomerular filtration rate in the elderly.Renal failure defined as a Cockgroft-Gault <30 mL/min is foundin 26.4% of the oldest-old admitted to an acute geriatric department. The elderly with renal failure is more often admitted for failure to thrive. No great differences were observed between renal function on admission and discharge. This revised version was published online in June 2006 with corrections to the Cover Date.     

Quantification of BK Viral Load in Asymptomatic Renal Allograft Recipients

Introduction: Polyoma BK virus (BKV) has recently been identified to cause renal allograft dysfunction, which manifests as polyomavirus-associated nephropathy (PVAN). However, the presence and level of BKV DNA in renal allograft patients with good and stable renal function have remained undetermined. Methods: In this prospective study, serum samples were collected from a total of 45 renal allograft recipients with serum creatinine <155 μmol/L. In 17 patients, whose duration of transplantation was under 2 years, samples were collected at 3–4-month intervals for up to 2 years after transplantation. BK viral load was quantified using quantitative polymerase chain reaction (Q-PCR). Results: The BK viral load in asymptomatic renal allograft recipients was independent of the duration of transplantation and did not correlate with allograft function. The mean (± SD) level of viremia was 552.80 ± 1931.00 genome copies/mL, with 92.9% of patients having low levels of viremia corresponding to <1 × 10³ copies/mL. In contrast, patients with proven PVAN had levels in the range of 10⁶ copies/mL. Conclusions: The prevailing BK viral load in asymptomatic renal allograft patients is quantifiably low. Our findings may guide optimal immunosuppressive modulation in PVAN cases, where judicious manipulation of immunosuppression is required without inciting allograft rejection.     

Significance of CD4 T-Cell Adenosine Triphosphate Levels Monitoring in Elderly Renal Transplant Recipients

ObjectivesTo find the significance of CD4 T-cell adenosine triphosphate (ATP) levels in elderly renal recipients in correlation with drug doses, levels, and clinical parameters.MethodsDrug doses and levels, CD4 T-cell ATP levesl (162 sequential samples), and other clinical data were collected and assessed among 31 elderly renal recipients who underwent transplantations from November 2007 to March 2011.ResultsAmong subjects with stable clinical status, the main ATP levels pretransplantation were not significantly different from those posttransplantation: 302.4 ± 97.5 ng/mL versus 288.8 ± 102.6 ng/mL (P > .05). There was no relationship between ATP levels and tacrolimus concentrations or doses. In 12 patients experiencing infection, the ATP levels were significantly lower then those of subjects showing a stable clinical status: 127.3 ± 92.8 versus 288.8 ± 102.6 ng/mL (P < .01). Six patients with biopsy-proven acute rejection episodes did not show significantly higher ATP levels compared with those who were clinically stable: 26.2 ± 224.8 versus 288.8 ± 102.6 (P > .05).ConclusionsCD4 T-cell ATP levels were valuable to monitor immunosuppression among elderly renal transplant recipients.     

Acute Sodium Chlorite Poisoning Associated with Renal Failure

Background and Objectives: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels. Design: Retrospective controlled study. Setting: Two tertiary Intensive Care Units. Patients: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50). Interventions: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment. Measurements and Results: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 ± 15.0 mmol/L for CVVHDF and 24.7 ± 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 ± 308 µmol/L vs. 326 ± 250 µmol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 ± 8.3 mmol/L vs. 14.1 ± 6.1 mmol/L; p = 0.0003, creatinine: 360 ± 189 µmol/L vs. 215 ± 118 µmol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 ± 9.0 mmol/L for CVVHDF vs. 16.7 ± 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 ± 167 vs. 211 ± 103 µmol/L, p < 0.0001) were better controlled in the CVVH group. Conclusions: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.     

Predictive Value of Bedside Effective Renal Plasma Flow for Renal Recovery in Severe Acute Renal Failure

Single injection, single blood sample, effective renal plasma flow (ERPF) estimated by^l3lI-orthoiodohippurate can be performed accurately and conveniently without urine collection at the bedside. The purpose of this study was to determine if ERPF early in the course of severe acute renal failure (ARF) predicts recovery of renal function in hemodynamically stable patients. Over 18 months, ERPF was determined in 33 such patients with ARF in whom an etiologic diagnosis could be established. Eight patients died within 2 months of onset and while on dialysis, did not have an autopsy, and were not considered further. Six patients (Group A) either remained on dialysis after at least 6 months follow-up or had irreversible renal disease at autopsy. In Group B (19 patients, 13 of whom were dialyzed), serum creatinine returned to less than 2.0 mg/dL (n = 16) or was decreasing without dialysis. Peak serum creatinine (Group A 11.2 ± 1.4; Group B 10.1 ± 1.3 mg/dL) did not differ between groups. Oliguria was present in 75% of Group A patients and in 25% of Group B patients. Initial ERPFs differed (p < 0.001) between Group A (90 ± 11) and Group B (204 ± 20 mL/min). Initial ERPF was greater than 125 mL/min in 15 Group B patients but in no Group A patients; the false-positive rate was 21% and the false-negative rate was 0%. We conclude that at a time when the etiology of ARF is often not established, an initial ERPF of 125 mL/min or greater predicts recovery of renal function and less than 125 mL/min suggests that renal function will not recover. Serial studies improve the diagnostic accuracy of this test.