ABSTRACT:Malakoplakia is an unusual granulomatous inflammatory disorder associated with diminished bactericidal action of leucocytes that occurs in immunosuppressed hosts. Cases of renal allograft malakoplakia are generally associated with a poor graft and patient survival. We present the case of a 56-year-old female with allograft and bladder malakoplakia occurring two years after renal transplantation complicated by an early antibody mediated rejection. Following a number of symptomatic urinary tract infections caused by resistant Gram-negative bacilli, a diagnosis of malakoplakia was made by biopsy of a new mass lesion of the renal allograft. Cystoscopy also revealed malakoplakia of the bladder wall. Immunosuppressant regimen was modified. Mycophenolate mofetil was ceased, prednisolone reduced to 5 mg/day and tacrolimus concentrations were carefully monitored to maintain trough serum concentrations of 2-4 μg/L. Concurrently, she received a prolonged course of intravenous antibiotics followed by 13 months of dual oral antibiotic therapy with fosfomycin and faropenem. This joint approach resulted in almost complete resolution of allograft malakoplakia lesions and sustained regression of bladder lesions on cystoscopy with histological resolution in bladder lesions. Her renal function has remained stable throughout the illness. If treated with sustained antimicrobial therapy and reduction of immunosuppression, cases of allograft malakoplakia may not necessarily be associated with poor graft survival. CASE REPORTWe present the case of a 56-year-old South-East Asian woman with renal allograft and bladder malakoplakia. She received a cadaveric renal transplant in March 2010 for IgA nephropathy. Prior to that she had received peritoneal dialysis for almost 4 years and underwent subtotal parathyroidectomy in October 2008. She was highly sensitized (Class 1 and 2 PRA 96%) due to earlier pregnancies and blood transfusions and the graft was mismatched at 6 of 6 HLA loci. Induction immunosuppression included basiliximab and IV methylprednisolone, followed by maintenance with tacrolimus (achieving trough levels 8.2-16.5 μg/L in the first month and 7-9 μg/L in the following 18 months), prednisolone (titrating down from 30 mg, once daily) and mycophenolate mofetil 720 mg, twice daily. She received Pneumocystis jirovecii (PJP) and cytomegalovirus prophylaxis with trimethoprim/sulfamethoxazole 800/160 mg, thrice weekly and valganciclovir 450 mg, daily for a period of 6 months.Postoperative course was complicated by biopsy-proven Grade 2 antibody mediated rejection that was treated with intravenous methylprednisolone, plasmapheresis and intravenous immunoglobulin, with resolution of serum creatinine to pre-rejection levels. She also developed newonset diabetes after transplantation (NODAT) that resolved after her corticosteroid dose was lowered.Although asymptomatic bacteriuria was documented on at least one occasion over the next year, she remained well until July 2011, when she presented with dysuria, fevers and pain over ...

The treatment of advanced renal cell carcinoma (RCC) remains a major therapeutic challenge for clinicians. Despite advances in the understanding of the immunobiology of RCC and the availability of several novel targeted agents, there has been little improvement in the survival of patients with metastatic RCC. This review will focus on the recent understanding of risk factors and treatment options and outcomes of metastatic RCC, in particular, targeted therapeutic agents that inhibit vascular endothelial growth factor and mammalian target of rapamycin pathways. Prospective studies are required to determine whether sequential targeted therapy will further improve progression-free survival in RCC. Ongoing research to develop novel agents with better tolerability and enhanced efficacy in the treatment of metastatic RCC is required.

CKD alone, in the absence of anaemia, does not predispose to increased risk of ABT or length-of-stay in patients with mild-to-moderate CKD undergoing elective joint surgery. However, low haemoglobin is associated with increased ABT utilization and increased length-of-stay. Considering that 1 in 4 patients undergoing elective hip or knee arthroplasty has CKD, optimal preoperative patient blood management may improve outcome in this population.

We present the case of an 80-year-old female admitted with multiple fragility fractures on a background of stage 4 chronic kidney disease (CKD). Baseline bloods revealed secondary hyperparathyroidism, hypocalcaemia and lownormal 25-hydroxy vitamin D (Table 1). She had never had a bone biopsy or bone densimetry, but osteoporosis was considered the most likely pathology given a parathyroid hormone (PTH) level within target, low-normal vitamin D levels, normal alkaline phosphatase (ALP) and an elevated baseline P1NP (serum type 1 procollagen) of 486 ug/L (normal range <90 ug/L). Her established CKD precluded bisphosphonate therapy, so the treating team elected to administer a 60 mg dose of denosumab subcutaneously. Post-treatment hypocalcaemia was anticipated, but the patient's low dose cholecalciferol (25 mcg daily) was mistakenly continued instead of transitioning to 1,25-dihydroxycholecalciferol as planned. Subsequently, the patient developed hypocalcaemic tetany day 4 postdenosumab, necessitating use of intravenous calcium gluconate. She was discharged with calcitriol 0.5 mcg four times a day (QDS), calcium carbonate 3 g three times a day (TDS) and plans for outpatient monitoring. Before this could eventuate, she was readmitted with altered mentation due to hypercalcaemia and required a further 13 day admission. Readmission values revealed a suppressed PTH; taken alongside the low-normal non-specific ALP, this might suggest induction of adynamic bone state as a result of high-dose vitamin D analogues and denosumab. Bone formation markers were, unfortunately, not re-assayed at that time.Denosumab is an anti-RANKL (nuclear factor-kappa B ligand) fully humanized monoclonal antibody, used in the management of osteoporosis and to prevent skeletal-related events in patients with metastatic malignancy.1 Favourable pharmacokinetics and lack of associated renal toxicity have popularized denosumab in CKD, despite sparse experimental data subject to criticism of study design 2,3 and no evidence of efficacy in CKD stages 4 and 5.4 Hypocalcaemia postdenosumab is common, with reported rates ranging from 5.5% to 20.8%. Pre-existing CKD is an independent risk factor for this, 1,2 presumably via induction of a 'hungry bone'-like state. The risk can be abrogated with use of high-dose calcium and vitamin D, and calcitriol is the preferred analogue in the CKD population. 5 Our case again illustrates a need for caution with denosumab in CKD, and the importance of close monitoring of serum calcium levels after induction of lowturnover states to avoid rebound hypercalcaemia.