Girish S Talaulikar

KHA‐CARI Guideline: Vascular access – central venous catheters, arteriovenous fistulae and arteriovenous grafts

Department of Nephrology, Monash Medical Centre, Department of Medicine, Monash University, Department of Radiology, Austin Health, Melbourne, Victoria, Department of Renal Medicine, Fremantle Hospital, Fremantle, Western Australia, Department of Nephrology, Royal Adelaide Hospital, Adelaide, South Australia, Department of Renal Medicine, The Canberra Hospital, Canberra, Australian Capital Territory, and Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia

Newer cardiac troponin I assays have similar performance to troponin T in patients with end-stage renal disease

Background: Troponin T is present in the blood of a majority of patients with endstage renal disease (ESRD) undergoing regular dialysis and presence of troponin T is a predictor of adverse outcome in these patients. With several new formulations of troponin I assays available, this study was performed to see whether these newer assays were able to detect troponin I in these patients more effectively than the older assays. Methods: One hundred and forty-three patients undergoing regular haemodialysis or peritoneal dialysis had plasma collected and troponin T and troponin I measured by a variety of assays. Results: The newer troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were able to detect troponin I (>75% of samples) as effectively as the Roche assay was able to detect troponin T, while other troponin I assays had a much lower rate of detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the troponin T assay had more samples detected at concentrations corresponding to an assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on the Bayer Centaur at 37%). Conclusions: Newer assays demonstrate that troponin I is present in a similar number of samples as is troponin T, in the blood of patients with dialysis-dependent renal failure, and these newer troponin I assays identify patients at risk of experiencing a cardiac event.

Outcome of Pregnancy in a Patient with Gitelman Syndrome: A Case Report

Gitelman syndrome (GS) is an autosomal-recessive condition characterized by hypokalaemia, hypomagnesaemia and hypocalciuria. Though it affects women of child-bearing age very little information is available about its impact on maternal and fetal outcome. We describe the course of pregnancy in a patient with GS which was characterized by a sixfold increase in potassium and magnesium requirements with inability to achieve normal levels despite intravenous supplementation. There was no adverse impact on the course of pregnancy or fetal outcome. The case highlights the variability in the phenotypic presentation of GS and recommends frequent monitoring of electrolytes with supplementation guided by clinical requirements without aiming to achieve normal blood levels.

Acute interstitial nephritis secondary to deferasirox causing acute renal injury needing short-term dialysis.

Transfusional siderosis affects many patients with iron loading anaemias and deferasirox, an oral iron chelator, is increasingly being used because of its efficacy and convenience. There have, however, been cases of renal failure associated with its use. Our report highlights this risk of renal injury and discusses its underlying pathology. A 70 year old man began to exhibit clinico-laboratory features of iron overload and cutaneous manifestations consistent with porphyria cutanea tarda (PCT). He was started on deferasirox as an iron chelator after attempts at venesection resulted in a fall in haemoglobin to 110 g/L. He also had multiple myeloma that had remained in partial remission with no significant changes in his serum electrophoresis ever since treatment with chemotherapy and stem cell transplant 5 years ago. Three weeks after deferasirox treatment, he presented with acute renal failure necessitating dialysis, and a renal biopsy showed features of tubulointerstitial nephritis (Fig. 1). Deferasirox was immediately discontinued and he was then treated with pulsed corticosteroids followed by oral prednisolone that resulted in prompt and sustained improvement in renal function which returned back to baseline. Although renal impairment has been noted with deferasirox in the earlier clinical studies, most resulted only in mild elevations in serum creatinine and presentations with acute renal failure requiring dialysis were uncommon. US Food and Drug Administration reports listed glomerulonephritis, interstitial nephritis and renal tubulopathy as possible causes of renal injury associated with deferasirox although detailed biopsy findings are lacking. Our suspicion of deferasirox as the aetiological cause for his acute interstitial nephritis is supported by his prompt response to treatment upon cessation of the drug. In addition, he had had no other exposure to new therapeutic agents over the prior months and other causes have been excluded. A single recent case report, however, has also shown biopsy-proven interstitial nephritis in a patient who was treated with deferasirox who promptly improved following cessation of the drug. The patient did not require dialysis support. Our case reinforces the link between deferasirox and acute interstitial nephritis as well as the spectrum of severity that can be seen. We also hope to highlight the need for vigilance when patients are started on it.

Allograft adenovirus nephritis

We present an uncommon case of allograft adenovirus tubulointerstitial nephritis in a 63-year-old male 6 weeks following cadaveric renal transplantation for end-stage renal failure secondary to hypertensive nephrosclerosis. The patient presented with acute onset of fevers, dysuria, haematuria and diarrhoea with acute graft dysfunction. A renal biopsy demonstrated necrotizing tubulointerstitial nephritis with viral cytopathic changes and no evidence of rejection. Adenovirus was identified as the pathogen. Treatment involved the reduction in the patients usual immunosuppression, intravenous immunoglobulin, piperacillin–tazobactam and ganciclovir. We present the clinical and pathological findings of necrotizing adenoviral nephropathy, highlighting the importance of considering this diagnosis in renal transplant recipients presenting with interstitial nephritis in the setting of a systemic illness.

Switchover to generic cyclosporine in stable renal transplant recipients: a single unit experience.

Background:u2003 The introduction of the immunosuppressant cyclosporine has significantly improved renal transplant survival. It is an expensive drug and generic alternatives may offer cost advantages. However, generic alternatives must be shown to provide equivalent therapeutic efficacy and safety. This study reports our experience of a switch from the microemulsion formulation of cyclosporine, Neoral (Novartis), to the generic equivalent, Cysporin (Mayne Pharma).

Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

BACKGROUNDnCalcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI.nnnOBJECTIVESnThis review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death.nnnSEARCH METHODSnWe searched the Cochrane Kidney and Transplant Specialised Register to 11 October 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.nnnSELECTION CRITERIAnAll randomised controlled trials (RCTs) where drug regimens containing CNI were compared to alternative drug regimens (CNI withdrawal, tapering or low dose) in the post-transplant period were included, without age or dosage restriction.nnnDATA COLLECTION AND ANALYSISnTwo authors independently assessed studies for eligibility, risk of bias, and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).nnnMAIN RESULTSnWe included 83 studies that involved 16,156 participants. Most were open-label studies; less than 30% of studies reported randomisation method and allocation concealment. Studies were analysed as intent-to-treat in 60% and all pre-specified outcomes were reported in 54 studies. The attrition and reporting bias were unclear in the remainder of the studies as factors used to judge bias were reported inconsistently. We also noted that 50% (47 studies) of studies were funded by the pharmaceutical industry.We classified studies into four groups: CNI withdrawal or avoidance with or without substitution with mammalian target of rapamycin inhibitors (mTOR-I); and low dose CNI with or without mTOR-I. The withdrawal groups were further stratified as avoidance and withdrawal subgroups for major outcomes.CNI withdrawal may lead to rejection (RR 2.54, 95% CI 1.56 to 4.12; moderate certainty evidence), may make little or no difference to death (RR 1.09, 95% CI 0.96 to 1.24; moderate certainty), and probably slightly reduces graft loss (RR 0.85, 95% CI 0.74 to 0.98; low quality evidence). Hypertension was probably reduced in the CNI withdrawal group (RR 0.82, 95% CI 0.71 to 0.95; low certainty), while CNI withdrawal may make little or no difference to malignancy (RR 1.10, 95% CI 0.93 to 1.30; low certainty), and probably makes little or no difference to cytomegalovirus (CMV) (RR 0.87, 95% CI 0.52 to 1.45; low certainty)CNI avoidance may result in increased acute rejection (RR 2.16, 95% CI 0.85 to 5.49; low certainty) but little or no difference in graft loss (RR 0.96, 95% CI 0.79 to 1.16; low certainty). Late CNI withdrawal increased acute rejection (RR 3.21, 95% CI 1.59 to 6.48; moderate certainty) but probably reduced graft loss (RR 0.84, 95% CI 0.72 to 0.97, low certainty).Results were similar when CNI avoidance or withdrawal was combined with the introduction of mTOR-I; acute rejection was probably increased (RR 1.43; 95% CI 1.15 to 1.78; moderate certainty) and there was probably little or no difference in death (RR 0.96; 95% CI 0.69 to 1.36, moderate certainty). mTOR-I substitution may make little or no difference to graft loss (RR 0.94, 95% CI 0.75 to 1.19; low certainty), probably makes little of no difference to hypertension (RR 0.86, 95% CI 0.64 to 1.15; moderate), and probably reduced the risk of cytomegalovirus (CMV) (RR 0.60, 95% CI 0.44 to 0.82; moderate certainty) and malignancy (RR 0.69, 95% CI 0.47 to 1.00; low certainty). Lymphoceles were increased with mTOR-I substitution (RR 1.45, 95% CI 0.95 to 2.21; low certainty).Low dose CNI combined with mTOR-I probably increased glomerular filtration rate (GFR) (MD 6.24 mL/min, 95% CI 3.28 to 9.119; moderate certainty), reduced graft loss (RR 0.75, 95% CI 0.55 to 1.02; moderate certainty), and made little or no difference to acute rejection (RR 1.13 ; 95% CI 0.91 to 1.40; moderate certainty). Hypertension was decreased (RR 0.98, 95% CI 0.80 to 1.20; low certainty) as was CMV (RR 0.41, 95% CI 0.16 to 1.06; low certainty). Low dose CNI plus mTOR-I makes probably makes little of no difference to malignancy (RR 1.22, 95% CI 0.42 to 3.53; low certainty) and may make little of no difference to death (RR 1.16, 95% CI 0.71 to 1.90; moderate certainty).nnnAUTHORS CONCLUSIONSnCNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.

Immune Thrombocytopenia after Renal Transplantation for IgA Nephropathy

Immune thrombocytopenic purpura associated with renal disease is usually therapy-related, occurring after administration of intravenous immunoglobulin therapy or anti-D. Secondary cases occurring after renal transplantation are extremely rare. We present the second reported case of immune thrombocytopenic purpura occurring after renal transplantation for IgA nephropathy. Primary IgA nephropathy is the most common form of primary glomerulonephritis and although the pathogenesis of the disease remains incompletely understood, recent evidence suggests that the basic abnormality lies within the IgA immune system rather than in the kidney. We postulate a novel mechanism for thrombocytopenia occurring in such cases.

Outcomes of cinacalcet withdrawal in Australian dialysis patients: Cinacalcet withdrawal in dialysis

Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres.

Erratum: KHA-CARI Guideline: Vascular access Central venous catheters, arteriovenous fistulae and arteriovenous grafts (Nephrology (2013) 18 (701-705))

10.1111/nep.12183 The authors would like to draw the readers’ attention to a mistake in the following article: Kevan R Polkinghorne, George K Chin, Rob J MacGinley, Andrew R Owen, Christine Russell, Girish S Talaulikar, Edwina Vale and Pamela A Lopez-Vargas. KHA-CARI Guideline: Vascular access – central venous catheters, arteriovenous fistulae and arteriovenous grafts. Nephrology 2013; 18: 701–705. Author Rob J MacGinley was affiliated with the wrong institution due to an oversight. The correct affiliation should be as follows. Department of Nephrology, Barwon Health, The Geelong Hospital, Geelong, Victoria, Australia. The authors apologise for this error and any confusion it may have caused bs_bs_banner