Gt John

Leflunomide for cytomegalovirus: bench to bedside

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality among transplant recipients, frequently engaging the clinician in a struggle to balance graft preservation with control of CMV disease. Leflunomide has been shown to have immunosuppressive activity in experimental allograft models together with antiviral activity inhibiting CMV both in vitro and in vivo. Data are emerging about its potential role in ganciclovir‐sensitive and ‐resistant CMV, primarily by virtue of a unique mechanism inhibiting virion assembly, as opposed to inhibition of viral DNA synthesis by current agents. This review aims to put in perspective, the knowledge acquired in the last decade or so on leflunomide for CMV. Evidence suggests that it might have activity against human CMV with good oral bioavailability and, more importantly in the resource‐poor setting, is economical. Although the data presented here are not from randomized trials, several relevant observations have been made that could influence future, more structured assessments of the drug. An immune suppressive compound with antiviral features and experimental activity in chronic rejection is an attractive combination for organ transplantation, and it appears that leflunomide may just fit that niche.

Leflunomide with low-dose everolimus for treatment of Kaposi’s sarcoma in a renal allograft recipient

Current treatment of Kaposis sarcoma is reduction of immunosuppression with or without addition of mammalian target of rapamycin inhibitors (mTORi). Akt signalling plays a central role in oncogenesis of Kaposis sarcoma. We describe a case of multifocal Kaposis sarcoma in a renal allograft recipient, which showed unsatisfactory early response to immunosuppression reduction along with everolimus therapy but completely resolved after adding leflunomide. mTORi impair Kaposis sarcoma oncogenesis by inhibiting mTOR downstream from the Akt signalling. Leflunomide inhibits Akt phosphorylation. This synergistic effect may be beneficial in treatment of Kaposi sarcoma and needs to be explored in trials.

Extensive emphysematous pyelonephritis in a renal allograft treated conservatively: case report and review of the literature.

Emphysematous pyelonephritis (EPN) is a rare occurrence in renal allografts. An aggressive approach resulting in transplant nephrectomy is viewed as the standard of care. Over the recent years, treatment with percutaneous drainage (PCD) of the renal and perinephric collections and appropriate antibiotics has been reported with good success in lesser grades of this infection. Only 4 cases of extensive EPN disease with Escherichia coli, treated with conservative management, are reported in the English‐language literature. We present a case of severe EPN caused by Klebsiella pneumoniae, successfully managed with early PCD, and propose a step‐up strategy aimed toward graft preservation.

Current concepts in C3 glomerulopathy.

Complement component 3 glomerulopathy (C3G) is a recently defined entity comprising of dense deposit disease and C3 glomerulonephritis. The key histological feature is the presence of isolated C3 deposits without immunoglobulins. Often masqueradng as some of the common glomerulonephritides this is a prototype disorder occurring from dysregulated alternate complement pathway with recently identified genetic defects and autoantibodies. We review the pathophysiology, clinical features, and diagnostic and treatment strategies.

A Randomized Controlled Trial to Determine the Appropriate Time to Initiate Peritoneal Dialysis after Insertion of Catheter (Timely PD Study)

Background: The optimal time for the commencement of peritoneal dialysis (PD) after PD catheter insertion is unclear. If dialysis is started too soon after insertion, dialysate leaks and infection could occur. However, by starting PD earlier, morbidity and costs can be reduced through lesser hemodialysis requirements. This is the first randomized controlled trial to determine the safest and shortest interval to commence PD after catheter insertion. Methods: All consecutive patients undergoing PD catheter insertion at the Royal Brisbane and Womens Hospital and Rockhampton Hospital from 1 March 2008 to 31 May 2013 who met the inclusion and exclusion criteria were invited to participate in the trial. Participants were randomized to 1 of 3 groups. Group 1 (G1) commenced PD at 1 week, group 2 (G2) at 2 weeks and group 3 (G3) at 4 weeks after PD catheter insertion. These groups were stratified by hospital and the presence of diabetes. Primary outcomes were the incidence of peritoneal fluid leaks or PD-related infection during the 4 weeks after commencement of PD. Results: In total 122 participants were recruited, 39, 42, and 41 randomized to G1, G2, and G3, respectively. The primary outcome catheter leak was significantly higher in G1 (28.2%) compared with G3 (2.4%, p = 0.001) but not compared with G2 (9.5%, p = 0.044), based on intention to treat analysis. These differences were even more marked when analyzed with per protocol method: G1 had a significantly higher percentage (32.4 %) compared with G3 (3.3%, p = 0.003) but not compared with G2 (10.5%, p = 0.040). Event percentages of leak were statistically higher in G1 and occurred significantly earlier compared with other groups (p = 0.002). Amongst diabetics, technique failure was significantly higher (28.6%) in G3 compared with 0% in G1 and 7.1% in G2 (p = 0.036) and earlier in G3 at 163.2 days vs 176.8 and 175.8 (p = 0.037) for G1 and G2, respectively. Conclusion: Leaks were higher in participants commencing PD at 1 week after catheter insertion compared with the other 2 groups, and technique failure was higher in diabetics starting PD at 4 weeks.

Epidemiology of biopsy-proven glomerulonephritis in Queensland adults.

There is a paucity of data pertaining to the incidence of biopsy‐proven glomerulonephritis (GN) in Australia. This retrospective study aims to review the data from all adult native renal biopsies performed in the state of Queensland from 2002 to 2011 – comparing results with centres from across the world.

A protocol for the identification and validation of novel genetic causes of kidney disease

BackgroundGenetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10xa0% of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD.Methods/DesignThis study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra-renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed.DiscussionThis investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology.

Dialysis and Pregnancy in End Stage Kidney Disease Associated with Lupus Nephritis

Female patients with systemic lupus erythematosus are often of childbearing age at diagnosis, and though fertility in these patients is similar to the general population, successful pregnancy remains a rare occurrence. This incidence is, however, increasing and the management of these high risk pregnancies is often further complicated by the patients need for dialysis as a result of lupus nephritis (LN). We share our experience in managing two LN patients with successful pregnancies, one on automated peritoneal dialysis and the other on haemodialysis, as well as a review of cases in the literature.

Ibuprofen-related renal tubular acidosis in pregnancy

Ibuprofen-related renal tubular acidosis (RTA) has not been previously described in pregnancy but its occurrence outside of pregnancy is being increasingly described. In this case, a 34-year-old woman presented in the third trimester of pregnancy with Type 1 or distal RTA related to ibuprofen and codeine abuse. It was complicated by acute on chronic renal dysfunction and hypokalemia. Delivery at 37 weeks gestation due to concerns of evolving preeclampsia resulted in the birth of a healthy neonate. RTA and hypokalemia were remediated and ibuprofen and codeine abuse ceased. Some renal dysfunction however continued. Thorough and repeated history taking as well as vigilance for this condition is suggested.

Jejunal Mesenteric Artery Laceration Following Blind Peritoneal Catheter Insertion Using the Trocar Method

Editor: Percutaneous peritoneal catheter insertion for peritoneal dialysis (PD) is widely used and success rates similar to those with open placement are reported. Percutaneous insertion is typically done using either a Seldinger technique or the Trocar method. We report a case where blind percutaneous catheter insertion using the Trocar method resulted in jejunal mesenteric arterial laceration and severe intra-abdominal bleeding. A 56-year-old man with diabetic nephropathy, chronic kidney disease stage 5, and ischemic heart disease presented with fluid overload. He was stabilized with ultrafiltration and hemodialysis over 2 weeks. A month later, he underwent blind percutaneous PD catheter insertion in which the trocar and cannula method was used. After a dose of preoperative intravenous vancomycin and sedation with intramuscular pentazocine, a midline incision 2.5 cm long was made about 2 cm below the umbilicus. The peritoneal cavity was filled with 1.5 L saline using an 18F intravenous cannula. The trocar and cannula were vertically maneuvered to make a point incision in the linea alba big enough to admit the lubricated permanent PD catheter, which was then secured in place by purse-string proline sutures. About 1 L PD fluid was instilled in the peritoneal cavity via the PD catheter. The drain was initially mildly blood tinged. The subcutaneous tunnel was made and the distal end of the catheter exteriorized. The incision wound was closed in layers. The effluent continued to be blood tinged and the patient’s blood pressure began to decrease. Despite two units of whole blood and fluids, the patient continued to be in hypovolemic shock. At laparotomy, the peritoneal cavity was filled with blood: a laceration of the jejunal mesenteric artery was identified and ligated. Further blood transfusions after surgery stabilized the patient. The catheter position and tunnel were left untouched. The laparotomy incision was made in the midline immediately below the incision made for catheter insertion. The patient subsequently underwent regular PD exchanges without any impediment to either inflow or drainage of PD fluid. This is the only such complication that has been experienced in over 30 percutaneous catheter insertions. Blind percutaneous PD catheter insertion is a relatively easy procedure that can be done by nephrologists without requiring a dedicated operation theater and anesthesia time. The procedure is safe when done by experienced personnel. There are two percutaneous techniques. The more common is the procedure using a peel-away sheath with the Seldinger technique (1). The other, using a trocar and cannula, is employed at our center. The laparoscopic and open surgical techniques require obtaining specialized surgical and anesthetic services, are more expensive, and increase the duration of hospital stay. The open surgical method is routinely preferred in those with prior abdominal surgeries with likelihood of adhesions. However, in the blind procedures, there always exists the unavoidable risk of misadventure and surgical backup is necessar y. The technique of catheter insertion using the peel-away sheath obviates the need of the sharp trocar and is less likely to cause injury to viscera. The fluoroscopy-guided procedure is perhaps safer and, although the two have not been directly compared, results and safety are comparable to the directly visualized surgical method (2). While the usefulness remains unproven, the surgical method has been more commonly employed in obese patients (3) and we began to adopt this practice after the occurrence of this complication. Minor hemorrhage following PD catheter placement is usually caused by abdominal wall blood vessel injury and can easily be controlled. Mital et al. (4) reported a retrospective case series of surgical placement of 292 catheters where there was major hemorrhage in 6 patients (2%). However, this was due to perioperative anticoagulation, aspirin use, or thrombocytopenia in all but 1 patient. Smith et al. reported the occurrence of bleeding associated with percutaneous placement of PD catheters in 2 of 31 (6.4%) catheter placements (5). Neither patient required exploration or blood transfusions but settled with PD fluid exchanges. One required transfusion of platelets for thrombocytopenia. When the effluent is bloody with hemodynamic compromise, as in our patient, immediate explorative