Jeffrey A J Barbara

Assessment of the Nova StatSensor whole blood point-of-care creatinine analyzer for the measurement of kidney function in screening for chronic kidney disease

Abstract Background: Point-of-care testing for creatinine using a fingerprick sample and resultant estimated glomerular filtration rate has potential for screening for chronic kidney disease in community settings. This study assessed the applicability of the Nova StatSensor creatinine analyzer for this purpose. Methods: Fingerprick samples from 100 patients (63 renal, 37 healthy volunteers; range 46–962 μmol/L) were assayed using two StatSensor analyzers. Lithium heparin venous plasma samples collected simultaneously were assayed in duplicate using the isotope dilution mass spectrometry-aligned Roche Creatinine Plus enzymatic assay on a Hitachi Modular P unit. Method comparison statistics and the ability of the StatSensor to correctly categorise estimated glomerular filtration rate above or below 60 mL/min were calculated pre- and post-alignment with the laboratory method. Results: StatSensor 1 creatinine results (y) were much lower than the laboratory (y=0.75x+10.2, average bias –47.3, 95% limits of agreement –208 to +113 μmol/L). For estimated glomerular filtration rates above or below 60 mL/min, 100% and 87% of results respectively agreed with the laboratory estimated glomerular filtration rate (79% and 96% post-alignment). StatSensor 2 statistics were similar. The 95% limits of agreement between StatSensor creatinine results were –35 to +34 μmol/L. Conclusions: Isotope dilution mass spectrometry alignment of the StatSensor will identify most patients with estimated glomerular filtration rate <60 mL/min, but there will be many falsely low estimated glomerular filtration rate results that require laboratory validation. Creatinine results need improvement. Clin Chem Lab Med 2010;48:1113–9.

Leflunomide for Inflammatory Arthritis in End-Stage Renal Disease on Peritoneal Dialysis: A Pharmacokinetic and Pharmacogenetic Study

OBJECTIVE To study the pharmacokinetics and pharmacogenetics of leflunomide and document its efficacy and safety in the treatment of inflammatory arthritis in a patient with end-stage renal disease (ESRD) who was on peritoneal dialysis. CASE SUMMARY Therapy for a 78-year-old man with ESRD who required peritoneal dialysis was started with leflunomide 10 mg/day for psoriatic arthritis. The dosage was increased to 20 mg/day after 3 months. Monitoring was continued until the patients unexpected death from myocardial infarction at 8 months. Total and unbound teriflunomide (the active metabolite of leflunomide) concentrations were measured by liquid-chromatography-tandem mass spectrometry. Genotyping for CYP2C19 and ABCG2 polymorphisms, both known to influence teriflunomide pharmacokinetics, was also performed. DISCUSSION Total concentrations of teriflunomide varied between 5.2 and 23.2 mg/L, while unbound concentrations varied between 0.0306 and 0.1468 mg/L. The unbound fraction varied between 0.367% and 0.71%. Teriflunomide was found in the dialysate at a concentration of 0.0981 mg/L. A single CYP2C19 loss of function allele was present, as was wild-type ABCG2. Leflunomide appeared to be therapeutically effective, as evidenced by a reduction in daily prednisolone dosage from 20 mg to 6mg; the Disease Activity Score in 28 joints (DAS28) was 5.46 at enrollment and 4.03 after 7 months. Health Assessment Questionnaire—Disability Index improved from 0.5 to 0.125 at 7 months. Numerous significant adverse events that were considered unrelated to leflunomide occurred. CONCLUSIONS Dose adjustment for leflunomide does not appear to be required in the context of ESRD requiring peritoneal dialysis. We present novel evidence that a small amount of teriflunomide is removed by peritoneal dialysis. This case suggests that leflunomide is safe to use as therapy for inflammatory arthritis despite the presence of ESRD requiring peritoneal dialysis.

Acute effects of haemodialysis on biochemical modulators of endothelial function

Objectives.  To assess the acute effects of haemodialysis (HD) on biochemical factors modulating endothelial function.

Human leucocyte antigen DQ alpha heterodimers and human leucocyte antigen DR alleles in tubulointerstitial nephritis and uveitis syndrome.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare clinical entity of acute interstitial nephritis (AIN) associated with uveitis. First described in 1975 by Dobrin et al., over 200 cases have been reported. Although the pathogenesis of TINU syndrome is unknown, the current view is that it is the result of an autoimmune process. Both cell-mediated immune responses and autoantibody production have been implicated. The association between TINU and human leucocyte antigen (HLA) phenotypes (DQ and DR) alleles has been the subject of several small studies. The authors review the literature and present two cases of definite TINU in an Australian population in which the same HLA DQA1*01, DQB1*05 and DRB1*01 haplotype was identified.

Effects of pre- vs. intra-dialysis folic acid on arterial wave reflections and endothelial function in patients with end-stage renal disease.

BACKGROUND Haemodialysis (HD) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [folic acid (F)] or impairing [asymmetric dimethylarginine (ADMA)] arterial function. Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD. We speculated that intra-HD, instead of pre-HD, F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss. METHODS Arterial wave reflections [augmentation index (AIx), pulse-wave analysis], endothelium-dependent vasodilation (salbutamol-mediated changes in AIx) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients (age 67.7 +/- 10.3 years). Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2-4 weeks apart, in an open-label randomized cross-over trial. RESULTS Pre-HD F administration did not prevent significant reductions in F during HD (end-HD vs. pre-HD, -865 +/- 465 nmol l(-1), P < 0.001), but no significant changes in AIx (+1.4 +/- 5.7%) or salbutamol-mediated AIx modifications (+0.4 +/- 5.5%) were observed. By contrast, intra-HD F administration was associated with significant increases in F (+298 +/- 283 nmol l(-1), P = 0.010) and a significant reduction of AIx (-4.7 +/- 7.2%, P = 0.013), but no effects on salbutamol-mediated AIx changes (+1.5 +/- 4.4%). There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration (P = 0.066). CONCLUSIONS Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD. Given the prognostic significance of arterial wave reflections in HD patients, the timing of F administration is important in the design of interventional trials in this cohort.

Symmetric Dimethylarginine is an Independent Predictor of Intradialytic Hypotension

BACKGROUND Hemodialysis (HD) is associated with significant reductions in the plasma concentrations of the nitric oxide (NO) inhibitors N(G)-monomethyl L-arginine (L-NMMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). We sought to determine whether elevated concentrations of these NO inhibitors pre-HD and/or their acute decrease during HD might mediate intradialytic hypotension (IDH). METHODS Systolic blood pressure (SBP), L-arginine, L-NMMA, ADMA, and SDMA were measured at the beginning (pre-HD) and at the end (end-HD) in 52 consecutive HD patients (age 64.4 +/- 13.4 years). IDH was defined as a SBP reduction of >20 mm Hg end-HD vs. pre-HD. RESULTS Fourteen patients demonstrated IDH. The mean SBP reduction during HD in this group was -35 +/- 13 mm Hg compared to an increase of +2 +/- 12 mm Hg among the 38 patients without IDH (no-IDH). Baseline demographic, clinical, and biochemical parameters did not differ between the IDH and no-IDH groups. However, the IDH group had higher pre-HD SBP (155 +/- 17 vs. 132 +/- 14 mm Hg, P < 0.001), pre-HD plasma SDMA concentrations (1.98 +/- 0.61 vs. 1.64 +/- 0.46 micromol/l, P = 0.04), and greater SDMA reductions during HD (-0.78 +/- 0.43 vs. -0.56 +/- 0.32 micromol/l, P = 0.06) than the no-IHD group. After adjusting for pre-HD SBP, the odds of IDH occurring were higher with increased pre-HD SDMA plasma concentrations (OR = 1.31 per 0.1 micromol/l SDMA increase; 95% CI = 1.04-1.65, P = 0.02) and with decreases in SDMA during HD (OR = 1.39 per 0.1 micromol/l SDMA decrease; 95% CI = 1.02-1.91, P = 0.04). CONCLUSION Increased pre-HD SDMA plasma concentrations and greater SDMA reductions during HD independently predict IDH after adjusting for demographic and clinical variables, pre-HD SBP, and other methylated forms of L-arginine.

Prevalence of Hypercalcaemia in a Renal Transplant Population: A Single Centre Study

Introduction. Postrenal transplant bone disease is a significant problem. Factors influencing postrenal transplant bone status include high dose acute and low dose long-term steroid use, persistent hypercalcaemia, and graft failure. In this study, we aimed to determine the prevalence of hypercalcaemia and to evaluate the risk factors for postrenal transplant hypercalcaemia in long-term renal transplant patients at our centre. Methods. This is a biochemical audit in which we studied renal transplant recipients from the Central Northern Adelaide Renal Transplant Services, South Australia. Inclusion criteria include kidney transplant patients with functioning graft since 1971 and at least 3 months after transplantation at the time of analysis. Hypercalcaemia was defined as persistently elevated serum corrected calcium greater than or equal to 2.56 mmol/L for three consecutive months. Results. 679 renal transplant recipients with a functioning graft were studied and 101 were hypercalcaemic between March 2011 and June 2011 (15%). 60% of the hypercalcaemic patients were male and 40% were female, with chronic glomerulonephritis (39%) being the commonest cause of their end stage kidney disease (ESKD). Prevalence was similar in those that had haemodialysis and peritoneal dialysis pretransplantation. Hypercalcaemia in the renal transplant population was not secondary to suboptimal allograft function but secondary to pretransplantation hyperparathyroidism with persistent high parathyroid hormone (PTH) levels after transplantation. Conclusion. There is a high prevalence of hypercalcaemia (15%) in renal transplant recipients. The predominant cause for hypercalcaemia is pretransplantation hyperparathyroidism. The magnitude of pretransplantation hyperparathyroidism is the major determinant for long-term parathyroid function rather than graft function or pretransplantation duration on dialysis or mode of dialysis.

Bilateral renal inflammatory pseudotumour effectively treated with corticosteroid

Inflammatory pseudotumour (IPT) is a rare disease of unknown cause that most commonly involves the lung but can occur in almost any site in the body. Occurrence in the kidneys is very rare and bilateral renal involvement even rarer. There are 34 previously reported cases in the English-language medical literature between 1966 and 2008. Herein we report a case of IPT infiltrating both kidneys. We have also reviewed the clinical features, radiological findings, treatment and outcome of renal IPT. Clinical features at presentation are commonly non-specific. Features on imaging are inadequate to make a diagnosis of IPT or to clearly distinguish it from malignancy. Consequently diagnosis has frequently been made after nephrectomy and on a few occasions with the aid of percutaneous or open biopsies. The majority of renal IPT (83%) have been treated with nephrectomy and those cases with bilateral IPT have received corticosteroids.

Methylated arginines and nitric oxide in end-stage renal disease: impact of inflammation, oxidative stress and haemodialysis

Abstract Objectives: To determine whether inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde, MDA) or haemodialysis (HD) affect associations between asymmetric (ADMA), symmetric (SDMA) dimethylarginine, NG-monomethyl-L-arginine (L-NMMA) and nitrite/nitrate (NOx) in end-stage renal disease (ESRD). Method: Metabolites were measured pre-HD, after 1 hour and end-HD in 40 ESRD patients (age 63 ± 14 years). Results: Positive associations between NOx and ADMA (p = 0.04), SDMA (p < 0.001) and L-NMMA (p = 0.04) were observed pre-HD. Associations weakened during HD but were not significantly influenced by CRP or MDA. Conclusions: HD, oxidative stress or inflammation did not significantly affect the positive associations between methylated arginines and NOx in ESRD.

JC viraemia in kidney transplant recipients: to act or not to act?

Human polyomaviruses have entered the domain of clinical decision-making in renal transplantation and this has coincided with the use of more potent immunosuppressive regimens. BK polyomavirus has predominated, resulting in nephropathy and ureteral strictures with the potential for graft loss [1]. JCV is a type of human polyomavirus, named with the initials of the patient from whom the virus was first isolated. JC polyomavirus is known to cause progressive multifocal leukoencephalopathy (PML) which has been reported in the renal transplant population [2]. Polymerase chain reaction (PCR) screening for BK polyomavirus in the early post-transplant period is routinely performed worldwide but is not known to occur for JC polyomavirus.