Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study.

BACKGROUND: Sepsis emerges as the leading risk factor for acute kidney injury (AKI) development in critically ill patients. Much effort has been invested so far on early diagnosis of AKI using promising biomarkers. This study aimed to determine whether urine alpha1-microglobulin (α1m), a lipocaline member previously used as an indicator of proximal tubular dysfunction, can early predict the development of sepsis-associated AKI (SAAKI) in critically ill patients. METHODS: A prospective, observational study was conducted in a single center Intensive Care Unit (ICU). Patients with normal renal function admitted to the ICU followed for sepsis and AKI development. Urine α1m levels were analyzed in pooled samples from 24-hour urine collections on sepsis onset and at various time points thereafter. The diagnostic performance of urine α1m was assessed using thenonparametriccalculation of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Among 286 critically ill patients admitted to our ICU in a year, 45 patients with sepsis met the inclusion criteria. SAAKI developed in 16 septic patients (35.6%). Urine α1m levels were significantly elevated in all septic patients (average value of all samples on the day of sepsis: 46.02 ± 7.17 mg/l) and showed a trend to increase in patients who finally developed SAAKI. The AUC for SAAKI prediction according to α1m urine levels 24-hours before SAAKI onset was 0.739 (sensitivity 87.5%, specificity 62.07%, cutoff level 47.9 mg/l). Urine α1m 24-hours before SAAKI, serum creatinine on sepsis onset and Acute Physiology and Chronic Health Evaluation II (APACHE II) score on sepsis onset emerged as the most powerful independent predictors of SAAKI. The combination of these three parameters improved the AUC for SAAKI prediction to 0.944. CONCLUSION: Urine α1m levels might help in the early prediction of SAAKI development and may prove useful biomarker. The pathogenetic implications of α1m in sepsis and SAAKI need further investigation. Hippokratia 2014; 18 (3): 262-268.

Twenty four-hour ambulatory blood pressure monitoring and lipid levels before, 3, 6 and 12 months after the onset of hemodialysis in chronic kidney disease patients: a pilot study.

BACKGROUND: Twenty four-hour ambulatory blood pressure (BP) monitoring (ABPM) is being increasingly used to evaluate the effectiveness of antihypertensive medications. We aimed to to investigate the incidence of "non-dippers" in ESRD patients before, as well after the initiation of hemodialysis, to evaluate whether start of hemodialysis is associated with a reduction in the use of antihypertensive drugs, and to correlate 24-hour ABPM with serum lipid levels, the use of lipid-lowering drugs (statins) and the development of the Metabolic Syndrome (MetS) in these patients. METHODS: Thirty patients scheduled to initiate hemodialysis (glomerular filtration rate <15 ml/min/1.73m(2)) were prospectively recruited. Twenty four-hour ABPM and lipid levels were recorded before (T0), as well as 3 (T1), 6 (T2) and 12 (T3) months after hemodialysis onset. RESULTS: A progressively significant (p=0.025) decrease in the use of antihypertensive medications was observed in 26 of 30 patients throughout the study, whereas the remaining four patients were not hypertensive during the same period. There was a progressive increase in the use of statins for the management of dyslipidemia (p=0.015). This increase in statin use was coupled with an increase in the prevalence of the MetS in the study population (p=0.040). Patients with daily BP <135/85 mm Hg had a lower incidence of new MetS compared with patients with daily BP >135/85 mm Hg (p=0.053). CONCLUSIONS: Patients initializing hemodialysis demonstrate a progressively increased incidence of dyslipidemia and MetS, as well as a reduction in the use of antihypertensive drugs. Optimal management of BP and dyslipidemias is essential to reduce the high cardiovascular morbidity and mortality rates in this high-risk population.

In vitro and in vivo cytogenetic effects of recombinant human erythropoietin on the frequency of sister chromatid exchanges alone or in combination with mitomycin C.

BACKGROUND: Erythropoietin (EPO) is a glycoprotein which has a main property, erythropoiesis, but its range of action in the human body is very wide. It has been suggested that EPO acts cytoprotectively for many cell lines against many toxic causes in vitro and in vivo. Our aim was to study the action of EPO on DNA of two cell types, human lymphocytes in vitro and on P388 ascites tumor cells inoculated in BDF1 mice in the presence and absence of the genotoxic agent mitomycin C (MMC). METHOD: The sister chromatid exchange (SCE) assay was used as it is a very sensitive, simple and rapid method for detecting DNA damage. Proliferation rate indices (PRI) and mitotic indices (MI) were also counted. RESULTS: EPO did not alter the SCE level when it acted alone on both cell lines. MMC as a potent genotoxic agent increased SCE levels in vitro and in vivo. EPO used in combination with MMC significantly decreased SCE levels and increased PRI and MI values induced by MMC alone both in vitro and in vivo. CONCLUSIONS: EPO acts protectively against the genotoxic potential of MMC, and this action may have clinical implications.

Brucellosis in dialysis patients. Does it exist?

BACKGROUND: Brucellosis is a zoonotic disease transmittable to humans. It is diagnosed either by isolation of Brucella organism in culture of blood or other sample types (e.g., bone marrow or liver biopsy specimens), or by a combination of serological tests and clinical findings. Dialysis patients constitute a special population group with an impaired autoimmune system and a propensity to develop infections, such as brucellosis. This paper presents the high incidence of brucellosis in our dialysis patients during last year, while there was not any zoonotic infection recorded in the previous at least 5 year period. METHODS-RESULTS: This is a retrospective study including 8 dialysis patients, undergoing renal replacement therapies (5 patients were on hemodialysis (HD) and 3 on peritoneal dialysis (PD)), who out of a total of 124 patients developed brucellosis, during the last year. Four patients were male and four female and their mean age was 67 +/- 9 years. Clinical presentation of Brucellosis infection was mild with low-grade fever and symptoms of influenza. All patients were living in places where animal brucellosis was prevalent. Infection was diagnosed on the basis of clinical symptoms and signs and with polymerase chain reaction (PCR) analysis of peripheral blood. The affected patients had consumed fresh unpasteurized milk and cheese and were treated with oral doxycycline and oral rifampicin for 6 weeks. All patients are in follow up for at least 1 year, during which there were no relapses. CONCLUSIONS: Brucellosis is a zoonotic disease that can occur in dialysis patients who are susceptible to infection under certain conditions. Our brucellosis patients lived in agricultural and veterinary areas and had consumed unpasteurized milk and cheese and insufficiently cooked meat derived from infected animals.

Attenuation of cytogenetic effects by erythropoietin in human lymphocytes in vitro and P388 ascites tumor cells in vivo treated with irinotecan (CPT-11).

Erythropoietin (EPO) is a protein widely used against drug induced anemia at cancer patients. Irinotecan (CPT-11) is a genotoxic topoisomerase I inhibitor. We investigated the genotoxic, cytostatic and cytotoxic effects of EPO in the presence and in the absence of CPT-11 in human lymphocytes in vitro and in ascites cells of P388 leukemia in vivo. The levels of genotoxicity, cytostaticity and cytotoxicity were evaluated in human lymphocytes in vitro, and in P388 ascites tumor cells in vivo. The results show that EPO is not genotoxic. Unlikely to EPO, CPT-11 caused severe genotoxic, cytostatic and cytotoxic effects by significantly increasing SCE levels and decreasing PRI and MI values in peripheral lymphocytes in vitro and in P388 ascites tumor cells in vivo. Adding EPO in human lymphocyte cultures in vitro and in P388 leukemia bearing mice in vivo in the presence of CPT-11 decreased SCEs levels and increased PRIs and MIs were observed compared with cells treated either in vitro or in vivo with CPT-11 alone, which shows that EPO protected cells from the toxic action of CPT-11. EPO's protective action on human peripheral lymphocytes in vitro and P388 cells in vivo from the topoisomerase I inhibitor CPT-11, lead us to propose it as a geno- and cytoprotective agent.

A tumor-like manifestation of extrapulmonary tuberculosis in a hemodialysis patient.

Though pulmonary tuberculosis (TBC) remains the commonest clinical presentation, extrapulmonary TBC is an increasingly important clinical problem. Among the extrapulmonary sites, primary liver tuberculosis seems to be an extremely rare location. Fewer than 100 cases of TBC hepatic abscesses have been reported whereas most of them have been originated from other sites, usually the lung and the gastrointestinal track. Therefore, in the absence of any particular symptom this infrequent location may lead to a delayed or missing diagnosis. The present study reports the difficulties in early diagnosis of an extrapulmonary TBC case, as it happened to a 53-year-old man with diabetic nephropathy who started on regular hemodialysis for 5 months. In such "atypical presentations" the clinicians should bear in their mind the possibility of the TBC occurrence, which usually responds well to the conventional antituberculous therapy.

The alteration of dialysate cancer antigen 125 concentration under a biocompatible bicarbonate peritoneal dialysis solution and the preservation of the mesothelial cell viability.

BACKGROUND: The importance to maintain the peritoneal membrane integrity for peritoneal dialysis (PD) patients by using biocompatible solutions (with low or no glucose as osmotic factor and low in glucose degradation products-GDPs, without lactate as a buffer and with normal pH) becomes progressively more evident. The aim of the present study was to investigate the clinical effects of a novel bicarbonate-based biocompatible PD fluid, evaluating the alteration in the concentrations of dialysate marker CA125, a glucoprotein indicator of mesothelial cell mass. PATIENTS AND METHODS; This is a single-center, prospective cohort study of 12 stable CAPD patients (4 women, 8 men), mean age 71.3 +/- of 6.01 years, mean PD duration 31.9 +/- 21.33 months, treated with the usual conventional PD solutions (with increased GDPs, low pH, and lactate as a buffer system). After a six-month period, the patients changed for the next six-month period into bicarbonate PD solutions (BicaVera, Fresenius), after which they returned into their previous schema of conventional solutions for another six months. The dialysate marker of CA125 was repeatedly estimated at the beginning of the study (T0), after six months phase with the bicarbonate solutions (T6), and at the end of study (T12), after the second six-month use of the conventional PD solutions. All the samples were taken at the end of a four-hour dwell of an exchange with PD solution 2.5% glucose. RESULTS: The dialysate mean value of CA125 at the beginning of the study (Td0-with conventional PD solutions) was 15.07 +/- 5.72U/mL. After six months with bicarbonate PD solutions, the mean CA125 value increased to 111.97 +/- 66.21U/mL, while the mean values dropped again to 22.72 +/- 16.06 U/mL at the end of the study, after the patients' return for another six months to the conventional solutions use. There was a statistically significant difference between the mean CA125 levels at the beginning (Td0) and the middle of the study (Td6; p = 0.00079) as well as between the mean levels of CA125 in the middle (Td6) and at the end of the study (Td12; p = 0.0014). In contrast, comparing the mean dialysate values of CA125 at the beginning (Td0) and at the end of the study (Td12), no statistically significant difference was revealed (p = 0.13). CONCLUSIONS: For the use of the bicarbonate-based PD, more biocompatible solutions for six months produced a statistically significant increase in the dialysate concentration of the mesothelial cell mass indicator CA125. The decrease at the end of the study of CA125 mean value at a level similar with that observed at the beginning, after the six-month period of the conventional PD solutions, indicates that the clinical use of the new bicarbonate-based PD solutions may have an advantageous role in the preservation of peritoneal cell mass, maintaining also the integrity and longevity of the peritoneal membrane.

Urological management of indinavir-associated acute renal failure in HIV-positive patients.

INTRODUCTION: Indinavir, a protease inhibitor that is commonly used to treat HIV infection, may cause crystal formation within the renal tubules when urine pH is above 3.5. Crystallization in the urine may lead to intrarenal crystal deposition and acute renal failure (ARF). AIM: To establish the beneficial urological management of acute renal failure caused by indinavir treatment of HIV/AIDS patients. PATIENTS--METHODS: Five HIV positive patients (four men, one woman) with a mean age of 32 years (range 28-36 years) were referred to our Department of Urology from an AIDS outpatient Clinic, because of the development of postrenal acute renal failure with continuously elevated creatinine and urea plasma levels after indinavir therapy. Among the initial therapeutic maneuvers, indinavir administration was interrupted for 1 week while bilateral double-J ureteral stents were inserted in all the HIV/AIDS patients, during the first 24-72 h to secure upper-tract drainage. Concurrently urine has been acidified by oral administration of the amino acid L: -methionine and oral fluid intake was increased. RESULTS: All the patients responded well to the treatment and their renal function was effortlessly restored to normal within a few days. CONCLUSION: HIV-positive patients receiving indinavir therapy might be complicated by acute renal failure, mainly due to intrarenal crystal deposition (tubules) or urolithiasis (postrenal obstruction). This adverse effect may simply manage by the discontinuation of indinavir administration, urine acidification, as well as the possible early insertion of bilateral double-J ureteral stents.

Continuous Erythropoietin Receptor Activator (C.E.R.A.) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II study.

This dose-finding, open-label study examined the potential of subcutaneous Continuous Erythropoietin Receptor Activator (C.E.R.A.) to correct anaemia at extended administration intervals in 61 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease (CKD) on dialysis. After a 4-week run-in, patients were randomised to C.E.R.A. 0.15, 0.30 and 0.45 microg/kg/week. Within these dose groups, patients were further randomised to once weekly, once every 2 weeks or once every 3 weeks treatment. Mean changes in haemoglobin (Hb) increased with increasing C.E.R.A. dose during a period of 6 weeks where no dose adjustments were permitted. The effect was independent of administration schedule. Erythropoietic responses were sustained until the end of the study (12 weeks) in all groups. In total, 90% of patients in the 0.30 microg/kg/week group and 79% in the 0.45 microg/kg/week group responded to treatment (Hb increase > or =1.0 g/dl), compared with 72% in the 0.15 microg/kg/week group. Faster median response time was associated with increasing dose (51, 38 and 31 days, respectively) and response was unrelated to administration frequency. C.E.R.A. was generally well tolerated. Our results suggest that 0.60 microg/kg twice monthly would be a suitable starting dose of C.E.R.A. for the initiation of anaemia correction in patients with CKD on dialysis. Phase III studies will confirm the feasibility of using C.E.R.A. at extended administration intervals in patients with CKD and anaemia.

Tuberculous spondylitis in patients with end-stage renal disease undergoing chronic hemodialysis therapy.

Tuberculosis of the spine is not rare in immunocompromised patients and particularly in those with end-stage renal disease (ESRD). Furthermore, the possible vascular compromise of the spinal cord in patients with diabetic nephropathy may result in symptoms of neurological involvement that could lead to deterioration and paralysis. We report a series of 4 patients with ESRD undergoing dialysis that developed tuberculous spondylitis of the thoracic spine. Diabetic nephropathy was the primary cause for chronic kidney disease in 2 patients; 3 of these patients were treated conservatively with anti-tuberculous medication and orthotic splints and were cured. The fourth patient with diabetes mellitus and clinically evident signs and symptoms of severe vascular insufficiency has additionally developed incomplete paraplegia. A complete sensory recovery and partial recovery of the hip flexors and abductors within 3 months occurred, following decompression of the spine and drainage of the abscess, in combination with long-term anti-tuberculous treatment and spinal orthosis.

Timely transfer of peritoneal dialysis patients to hemodialysis improves survival rates.

AIMS: The two main renal replacement therapies (RRT)--hemodialysis (HD) and peritoneal dialysis (PD)--have been considered to be antagonistic in most published studies on the clinical outcomes of dialysis patients. Recently, it has been suggested that the complementary use of both modalities as an integrated care (IC) strategy might improve the survival rate of end-stage renal disease patients. The aim of this study was to estimate the final clinical outcome of PD patients when they transfer to HD because of complications related to PD. MATERIALS AND METHODS: We retrospectively analyzed data from the following patients that started RRT during the last 10 years: 33 PD patients (IC group; age 55 +/- 15 years, mean +/- SD) who transferred to HD, 134 PD patients (PD group, age 64 +/- 11 years) who remained in PD, and 132 HD patients (HD group, age 48 +/- 16 years) who started and continued in HD. The main reasons for the transfer to HD were relapsed peritonitis and loss of ultrafiltration, while various comorbid risk factors were adjusted by Cox hazards regression model (age, presence of diabetes or/and cardiovascular disease, serum hemoglobin and albumin levels, as well as the modality per se). RESULTS: 3- and 5-year survival rates for the IC, PD and HD groups were 97% and 81%, 54% and 28%, and 92% and 83%, respectively. The 5-year survival rate was significantly higher in IC patients than in PD patients (p < 0.00001) but, was not different from that in HD patients. CONCLUSIONS: Our results show that the IC of dialysis patients undergoing RRT improves the survival of patients on PD if they are transferred to HD upon the appearance of PD related complications.

Peritoneal catheter exit-site infections: predisposing factors, prevention and treatment.

Catheter-related infections, exit-site-tunnel infections and peritonitis remain the Achilles heel of peritoneal dialysis. Although the overall incidence of peritoneal-dialysis-related infectious complications has been reduced since the introduction of the Y-set and double bag system, approximately one-fifth of peritonitis episodes are associated with catheter exit-site and tunnel infections. Since its development in 1968, the Tenckhoff catheter has become one of the most widely used peritoneal catheters, and many have proposed that a number of modifications have made it a better choice. Controversies concerning the effect on exit-site infections of catheter(s) with one or two cuffs, with straight, coiled, Swan-Neck, or other modifications led to the randomized controlled studies that are reviewed in this paper. Several studies have confirmed that mupirocin, applied at the exit-site as part of regular exit-site care, reduces the risk of S. aureus exit-site and tunnel infections. Recently, the emergence on a world-wide basis of mupirocin-resistant S. aureus (MuRSA) in peritoneal dialysis patients has brought this prophylactic strategy into question. However the low frequency of resistant organisms after four years of mupirocin prophylaxis suggests that we can continue its use with annual surveillance. Once established, exit-site infections may respond to appropriate treatment, but if not the only option may be catheter removal and replacement. Although peritonitis risk has decreased over the past decade, mainly due to improvements in connection technology, exit-site and tunnel infections have not. An exit-site infection that does not respond to treatment may lead to tunnel infection and to persistent peritonitis, which may require catheter removal and occasionally discontinuation of the peritoneal dialysis. Therefore it is important to be familiar with these factors that predispose to exit-site infection and to know how to prevent and to treat such infections. This review will discuss factors that predispose to catheter-related exit-site infections, techniques of exit-site care, and ways to prevent exit-site infection, with emphasis on S. aureus infections and their treatment.

Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients.

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.

Long-term survival with peritoneal dialysis in ESRD due to diabetes.

Several clinical studies have evaluated the factors that affect survival rates and compared outcomes between CAPD and HD in diabetic patients. However, only a small number of diabetic PD patients have been followed for over 5 years, largely because of coexisting, far-advanced, target organ damage at the initiation of dialysis and its progression during the course of dialysis, the presence of various comorbid conditions at the start of dialysis and finally, the limitations of long-term PD. Among the various modes of renal replacement, many clinicians have favored continuous ambulatory peritoneal dialysis (CAPD) for the management of diabetic patients for several reasons. However, survival of diabetic patients undergoing peritoneal dialysis (PD) and hemodialysis (HD) is probably similar, while diabetics on CAPD have a lower actuarial survival and technique success rates than non-diabetic patients of comparable age. This paper reviews the literature and our experience concerning the long-term survival on peritoneal dialysis of diabetic patients with ESRD.

Peritoneal dialysis: better than, equal to, or worse than hemodialysis? Data worth knowing before choosing a dialysis modality.

Technological advances such as those that allow the delivery of an adequate dialysis dose to a larger percentage of patients, minimization of peritoneal membrane damage with more biocompatible solutions, and lower peritonitis rates will undoubtedly improve retention of patients on peritoneal dialysis (PD) for longer periods. Currently, only 15% of the world dialysis population is managed by PD. Peritoneal dialysis has many advantages over hemodialysis, and if end-stage renal disease (ESRD) patients are fully informed about them, the proportion of patients who would prefer this treatment would rise to 25%-30%. An integrated approach to the treatment of ESRD could start with PD in a large percentage of patients, especially those who will receive a kidney transplant within 2 - 3 years. With the present epidemic of ESRD, this approach could lead to a significant saving, relieve the pressure on dialysis units, and allow a larger number of ESRD patients to be treated.

Prevention of catheter related infections in patients on CAPD.

Catheter-related infections remain a serious problem for patients on peritoneal dialysis. Such infections can be reduced by careful patient selection and training, by the use of the best connection technology and screening and treating nasal carriage. To date, treatment is less than optimal and therefore, the primary goal should be prevention of catheter-related infections. Prevention is based on improving catheter design and implantation technique, while providing careful exit-site care. Regardless of how it is implemented, we must aggressively pursue the prevention of catheter-related infections by eradicating S. aureus exit-site carriage in PD patients. Based on its effectiveness in adult PD patients, its low rate of adverse effects, and its reasonable cost-effectiveness, application of mupirocin ointment at the exit-site is the current method of choice for preventing PD catheter infections caused by S. aureus. In addition to reducing S. aureus exit-site infections, mupirocin seems to reduce the rates of staphylococcal peritonitis and PD catheter loss. Whether the ointment should be applied in the nares, to the exit-site or both, and whether it should be used only in staphylococcal nasal carriers or all PD patients requires further study.