Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of contrast-induced nephropathy after computed tomography.

Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury (AKI) and a source of significantly increased short- and long-term mortality. Studies of large cohorts have revealed that more than half of these cases are in subjects undergoing cardiac catheterization and intra-arterial coronary angiography, and nearly a third follow computed tomography (CT) scans. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early predictive troponin-like biomarker for AKI. Its role in the timely diagnosis of CIN has already been examined in adults and children undergoing coronary angiography and a meta-analysis revealed a very good performance of plasma or urine NGAL in the prediction of CIN. Much of these data have been extrapolated to patients receiving intravenous (IV) contrast agent for CT scans, although major differences in patient populations, contrast volume administered and intra-procedural complications between the two settings exist. In this context, a recent prospective study by our group evaluated plasma NGAL, measured using standardized Τriage® NGAL test (Biosite Incorporated, San Diego, CA) at baseline and 6-h post-procedure, for early detection of CIN among hospitalized patients undergoing elective contrast-enhanced CT. CIN, defined as an increase in serum creatinine (SCr) of >25% or >0.5 mg/dL from baseline within 48-h post-procedure, was found in 8.51% of subjects. In contrast, significant elevation of plasma NGAL was found at 6-h post-procedure with excellent performance characteristics. This review presents the current status of NGAL in the prediction of CIN after IV contrast administration among hospitalized patients undergoing elective contrast-enhanced CT.

Encapsulating peritoneal sclerosis with favorable outcome in hemodialysis: an unusual case with a literature review.

Encapsulating peritoneal sclerosis is a rare condition of a poorly understood pathogenesis with recognized risk factors, such as medications, surgical interventions, systemic diseases, and malignancies. In endstage renal disease it has been associated with chronic peritoneal dialysis. We hereby report the case of a 59-year-old male hemodialysis patient, who was never treated with peritoneal dialysis and developed an unexplained massive ascites 4 months post laparoscopic cholecystectomy for gallstones. A second laparoscopy and histological evaluation revealed encapsulating peritoneal sclerosis-like findings with parietal peritoneum and spleen involvement. The patient was successfully treated for 12 months with prednisone and tamoxifen. Possible pathogenetic mechanisms of the disease in this case are discussed including peritoneal irritation by chronic cholecystitis, low-grade inflammation of hemodialysis, intraoperative complications and the hypothetical role of oxidized regenerated cellulose used for hemostasis. In conclusion, the suspicion of peritoneal sclerosis should be encountered in cases of unexplained ascites in patients undergoing hemodialysis. The early diagnosis includes laparoscopy and histological evaluation and can result in a good outcome under medical treatment; otherwise, there is a high possibility of bowel obstruction with fatal outcome.

Use of electron-beam sterilized hemodialysis membranes is not associated with significant and persistent thrombocytopenia.

Significant thrombocytopenia following hemodialysis with electron-beam (e-beam) sterilized membranes has been recently reported in a large-scale Canadian study. However, the underlying mechanism and the clinical significance of this finding remain undetermined as yet. We prospectively evaluated for a 4-month period the thrombocytopenic effect of the e-beam sterilized dialyzers as compared to the steam sterilized ones in two groups of well-controlled hemodialysis patients. There were no significant differences in pre- and post-dialysis platelet counts of patients using e-beam-sterilized dialyzers compared to those using steam-sterilized ones. Furthermore, no statistically significant differences between pre- and post-dialysis platelet counts were found throughout the study in the e-beam-sterilized group. However, 1 out of 9 patients demonstrated significant post-dialysis thrombocytopenia in 2/4 measurements. In conclusion, our study data do not support a continuously occurring thrombocytopenic effect in patients dialyzed with e-beam sterilized membranes. Further studies are needed to determine whether and how the use of e-beam sterilization may impact the interaction between certain membranes and platelets.

Chronic kidney disease epidemiology collaboration equation accuracy in predicting peritoneal dialysis-delivered creatinine clearance.

INTRODUCTION: Measuring total (residual kidney plus peritoneal) creatinine clearance (CrCl) with 24-h urine and dialysate collections is recommended for peritoneal dialysis (PD) adequacy evaluation. Prediction equations applied in this instance could simplify the approach. Cockcroft-Gault and modification of diet in renal disease (MDRD) four (MDRD-4) and six (MDRD-6) variables equations have been tested in this setting, and conflicting results have been reported. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is currently considered to be more sensitive than the established equations for kidney function estimation. However, its performance in PD adequacy evaluation has not been studied. Our aim was to assess CKD-EPI equation's performance in predicting total measured CrCl (MCC) in PD patients. MATERIAL AND METHODS: A group of 23 consecutive PD patients, male/female: 5/18, median age: 66 (32-91) years, median time on PD 32 (2-126) months, were enrolled in the study. All were treated by automated PD (APD). Sixteen out of twenty-three had residual renal function (RRF). MCC was determined from 24-h dialysate and urine collections and also predicted by Cockcroft-Gault, MDRD (4 and 6), and CKD-EPI equations. RESULTS: CKD-EPI and MDRD-6 estimation results were similar to MCC (9.01 ± 3.90 and 9.54 ± 2.98 vs. 8.64 ± 3.75 mL/min/1.73 m(2) p = 0.49 and 0.09, respectively). Neither the presence nor the volume of residual urine affected the accuracy of prediction. Cockcroft-Gault and MDRD-4 equations differed significantly from MCC and were not accurately predictive. CONCLUSION: CKD-EPI equation could be used with accuracy for predicting MCC in PD patients. Only MDRD-6 showed similar accuracy, whereas MDRD-4 and Cockcroft-Gault equations were found to be inappropriate in this setting.

Treatment with oral paricalcitol in daily clinical practice for patients with chronic kidney disease stage 3-4: a preliminary study.

BACKGROUND: Active vitamin D is an effective treatment for secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients often complicated by hypercalcaemia and hyperphosphataemia. Treatment with paricalcitol, a selective vitamin D receptor activator, has shown benefits by adequately reducing parathyroid hormone (PTH) levels with minimal changes in serum calcium (Ca) and phosphorus (P). The purpose of this study is to present data on the use of oral paricalcitol in real-life clinical practice in patients with CKD stage 3-4 and SHPT. METHODS: We studied 43 patients, M/F: 25/18, median age: 74 years (47-87), CKD stage 3/4: 16/27, with SHPT, who were prescribed oral paricalcitol at recommended doses for 6 months. Monthly measurements of serum intact PTH (iPTH), Ca, P, alkaline phosphatase (ALP), haemoglobin, albumin (ALB), lipid profile, proteinuria and 24-h urine creatinine clearance were performed 3 months before and 6 months after treatment initiation. RESULTS: Paricalcitol induced a significant, early and sustained, through the end of follow-up period, decrease in iPTH and ALP levels and an increase in serum ALB. No significant increase in Ca and P levels as well as in Ca × P product was observed during the study period. No significant changes were found in protein excretion, kidney function and the other measured parameters between baseline and last evaluation. Paricalcitol final median dose was 5 µg/week ranging between 3 and 7 µg/week. CONCLUSIONS: In the context of real-life clinical practice, oral paricalcitol for 6 months is an effective, well-tolerated treatment of SHPT in CKD stage 3-4 with minimal effects on calcium and phosphorus metabolism.

Plasma neutrophil gelatinase-associated lipocalin (NGAL) as an early predictive marker of contrast-induced nephropathy in hospitalized patients undergoing computed tomography.

BACKGROUND: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) represents a promising biomarker for AKI. Its role in the early diagnosis of CIN has already been examined in adults and children undergoing coronary angiography. This study was designed to prospectively evaluate plasma NGAL compared with serum creatinine (SCr) for early CIN detection among hospitalized patients undergoing contrast-enhanced computed tomography (CT). METHODS: We prospectively enrolled consecutive hospitalized patients undergoing elective CT with intravenous (IV), low-osmolar contrast administration. Patients with pre-procedure SCr >150 µmol/L (1.7 mg/dL), congestive heart failure, haemodynamic instability, sepsis, or urinary tract infection were excluded. Plasma NGAL was measured using the standardized Triage(®) NGAL test (Biosite Incorporated, San Diego, CA, USA) at baseline and 6 h post-procedure. SCr, blood urea nitrogen (BUN), albumin and sodium (Na) were measured and eGFR MDRD4 was calculated at the same intervals, as well as at 24 and 48 h post-procedure. CIN was defined as an increase in SCr of >25% or >44 µmol/L (0.5 mg/dL) from baseline within 48 h post-procedure, in the absence of other obvious causes. RESULTS: Forty-seven patients, male/female 27/20, median age 68 (31-88) years, 16/47 diabetics, with baseline SCr 91.94 ± 20.33 µmol/L (1.04 ± 0.23 mg/dL) and eGFR MDRD4 68.40 ± 18.22 mL/min/1.73 m(2) were enrolled. A contrast volume of 120 mL (range 100-150 mL) was administered. CIN was found in four subjects (8.51%), but detection by SCr was only possible 24 h in 1 and 48 h post-procedure in three. In contrast, significant elevation of plasma NGAL was found at 6 h post-procedure in those with versus those without CIN (779.25 ± 361.49 versus 82.30 ± 40.64 ng/mL, P < 0.001). Using a cutoff value of 200 ng/mL, sensitivity, specificity and area under the receiver-operating characteristic (ROC) curve of 6-h plasma NGAL for CIN prediction were excellent (100, 100 and 1.00%, respectively). Subjects with CIN did not differ in baseline demographics, renal function and diabetes status compared with those without CIN. No differences in any variable were noted between diabetics and non-diabetics. Plasma NGAL at 6 h (R (2) = 0.24, P < 0.001) was found to be an independent predictor of CIN. CONCLUSIONS: Plasma NGAL 6 h after contrast administration measured by the rapid, point-of-care Triage(®) NGAL test appears to be a useful biomarker in the early prediction of CIN among hospitalized patients undergoing elective contrast-enhanced CT. However, the small sample size and the very small number of CIN events are important limitations. In any case, according to our evaluation, CIN incidence in this well-controlled population underlines the importance of early detection by an adequate and simple procedure such as the 6-h plasma NGAL test.

New insights into uric acid effects on the progression and prognosis of chronic kidney disease.

Hyperuricemia is particularly common in patients with arterial hypertension, metabolic syndrome, or kidney disease. Its role, however, as a risk factor for both renal and cardiovascular outcomes and in the context of the well-established interrelationship between cardiovascular disease and chronic kidney disease (CKD) is debated. For decades high serum uric acid levels were mainly considered the result of renal dysfunction and not a true mediator of renal disease development and progression. However, recent epidemiological studies suggest an independent association between asymptomatic hyperuricemia and increased risk of arterial hypertension, CKD, cardiovascular events, and mortality. Furthermore, data from experimental models of hyperuricemia have provided robust evidence in this direction. Hyperuricemia causes increased arterial pressure, proteinuria, renal dysfunction, and progressive renal and vascular disease in rats. The main pathophysiological mechanisms of these deleterious effects caused by uric acid are endothelial dysfunction, activation of local renin-angiotensin system, increased oxidative stress, and proinflammatory and proliferative actions. A small number of short-term, single-center clinical studies support the beneficial influence of pharmaceutical reduction of serum uric acid on total cardiovascular risk, as well as on renal disease development and progression. Hyperuricemia is probably related to the incidence of primary hypertension in children and adolescents, as serum uric acid lowering by allopurinol has an antihypertensive action in this group of patients. Finally, it is clear that adequately powered randomized controlled trials are urgently required to elucidate the role of uric acid in cardiovascular events and outcomes, as well as in the development and progression of CKD.

Approaches to prolong the use of uncuffed hemodialysis catheters: results of a randomized trial.

BACKGROUND: Use of uncuffed catheters (UCs) in hemodialysis patients is common practice. An antibiotic lock has been recommended to prevent catheter-related bacteremia (CRB), although insufficient data are available about the appropriate antimicrobial agent and dose with prolonged use of UCs. METHODS: This open-label randomized study was conducted to compare gentamicin/heparin (group A) and taurolidine/citrate (group B), as catheter-lock solutions, in 119 chronic hemodialysis patients in whom a total of 150 UCs were placed. A well-matched historical control group (heparin) included 67 UCs in 58 patients (group C). RESULTS: CRB episodes developed in 6 and 8 patients in groups A and B, respectively, significantly fewer than in group C (20 patients). Cumulative CRB-free catheter survival at 90 days was 82% for A and 78% for B, which is significantly higher than the 26% for C. Similar Gram-positive infection rates were found in all groups. The Gram-negative infection rate was significantly lower in B compared to C. No significant differences in thrombosis rates were observed between the groups. CONCLUSIONS: Gentamicin/heparin and taurolidine/citrate, used for locking UC, were similarly effective at preventing CRB and catheter thrombosis for up to 3 months, until a functional permanent vascular access became available. Both antimicrobial lock solutions were superior to heparin in CRB prevention with similar thrombosis rates.

Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients.

Sevelamer hydrochloride (SH) has been reported to aggravate metabolic acidosis and hyperkalemia. This study was performed to evaluate acid-base status and serum potassium changes after replacing SH with lanthanum carbonate (LC) in hemodialysis patients. SH was prescribed for 24 weeks in 14 stable hemodialysis patients and replaced by LC in a similar treatment schedule. Laboratory tests, including indices of acid-base status, nutrition, bone/mineral metabolism, and dialysis adequacy, were performed monthly during the study. Dialysate bicarbonate, potassium and calcium concentrations remained constant. Serum bicarbonate and pH rose, and serum potassium dropped significantly under LC. Alkaline phosphatase also decreased significantly under LC. No significant differences were observed in the other studied parameters between the two treatment periods. Control of serum phosphate was similar under both phosphate-binders and no differences were observed in calcium, Ca × P product, CRP, or lipid levels. Dialysis adequacy was constantly kept within K/DOQI target-range. Although full compliance to treatment was reported, three patients on LC complained of gastrointestinal upset and/or a metallic taste, and four had difficulty chewing the LC tablet. LC improves metabolic acidosis and hyperkalemia in hemodialysis patients previously under SH. Although both medications are well-tolerated, the gastrointestinal side-effects appear to occur more frequently with LC; a fact that, together with difficulties in chewing the tablet, may result in decreased compliance.

IgA nephropathy in association with Crohn's disease: a case report and brief review of the literature.

A case of immunoglobulin A nephropathy (IgAN) complicating a 10-year history of biopsy-proven Crohn's disease in a 31-year-old man is described. The patient presented with mild proteinuria and impaired renal function in the setting of an exacerbation of Crohn's disease. Renal biopsy showed IgAN. The patient responded to steroid treatment with clinical remission of the bowel disease and improvement of renal function, while proteinuria remained unchanged. IgA glomerulonephritis is rarely associated with Crohn's disease with only a few previously described cases. We briefly review these cases together with an overview of potential pathophysiological connections between these two diseases.

Effects of interleukin-6 on depression risk in dialysis patients.

BACKGROUND/AIMS: Depression represents the most frequent psychiatric disorder in nephrology. Cytokines, and especially IL-6, were found to be elevated in depressed patients with normal renal function. The objective of this pilot study was to examine the relationship between depression and cytokines (IL-6, TNF-alpha, and IL-10) in patients with end-stage kidney disease (ESKD). METHODS: We studied 44 stable patients with ESKD for 71 +/- 66 months (32 males; 64 +/- 13 years; 27 on hemodialysis and 17 on peritoneal dialysis). The control group included 20 healthy age- and gender-matched individuals (12 males; 60 +/- 12 years). Depression was assessed by the Zung Self-Rating Depression Scale (ZS). Nephelometry for high-sensitivity CRP and ELISA kits for IL-6, IL-10 and TNF-alpha were used. RESULTS: Compared to controls, patients with ESKD had higher ZS scores (56.8 +/- 16.8 vs. 44 +/- 12.7, p < 0.01), WBC (7,987 +/- 2,347 vs. 6,413 +/- 870/mm(3), p < 0.01), ESR (36.3 +/- 15.8 vs. 9.4 +/- 3.3 mm, p < 0.001), TNF-alpha (52 +/- 18.4 vs. 10.7 +/- 2.8 pg/ml, p < 0.001) and IL-6 (6.3 +/- 4 vs. 1.8 +/- 0.4 pg/ml, p < 0.001). No differences in high-sensitivity CRP and IL-10 were noted between the ESKD and control groups. Serum IL-6 levels were the only parameter positively correlated with the values of the ZS score in ESKD patients (r = 0.34, p < 0.02). CONCLUSIONS: IL-6 may play a role in the pathogenesis of depression in patients with ESKD.

Inflammation and oxidative stress in end-stage renal disease patients treated with hemodialysis or peritoneal dialysis.

PURPOSE: The impact of different dialysis modalities on oxidative stress and inflammation and the factors implicated in this interrelationship have not been adequately studied. This study was designed to comparatively evaluate the effect of hemodialysis (HD) and peritoneal dialysis (PD) on oxidative stress and inflammatory biomarkers and to search for associated factors. METHODS: We studied 20 HD, 11 PD patients and 11 healthy controls. Calculations were based on total antioxidant capacity (TAC) and superoxide dismutase (SOD), by spectrophotometry, as oxidative stress biomarkers; and high sensitivity CRP (hs-CRP), Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha), by ELISA, as inflammation biomarkers. RESULTS: HD and PD patients showed significantly increased levels of TA C, SOD and hs-CRP compared to healthy controls. No significant difference was observed in TNF-alpha and IL-6. Compared to HD patients, PD patients showed TNF-alpha levels that were increased, although non-significantly, and significantly higher homocysteine (Hcy). No differences were observed for IL-6, hs-CRP, TA C and SOD. In HD patients, significant positive correlations were found between intact parathyroid hormone (iPTH) and TNF-alpha, and between uric acid (UA) and TAC. Beta2-microglobulin (Beta2M) was negatively correlated with TAC, total cholesterol (TC) positively with TNF-alpha and negatively with SOD, and triglycerides (TG) correlated positively with TNF-alpha. In PD patients, TG correlated positively with TNF-alpha, HDL-cholesterol negatively with TNF-alpha, LDL-cholesterol negatively with SOD, and Beta2M negatively with SOD. CONCLUSIONS: HD and PD patients show similar degrees of inflammation and oxidative stress activation. Factors such as UA, iPTH, Beta2M and lipid profile correlate to oxidative stress and inflammatory biomarkers in both HD and PD patients.