David M Gracey

Tenofovir-associated Fanconi syndrome in patients with chronic hepatitis B monoinfection.

Tenofovir disoproxil fumarate (TDF) is increasingly used in patients with chronic hepatitis B (CHB) infection. Although associated with renal toxicity in HIV-infected patients, renal dysfunction has been reported rarely in the monoinfected CHB population. To date, TDF-associated Fanconi syndrome has not been reported. Here, we present two cases of TDF-associated Fanconi syndrome with rapid resolution after its cessation. We then discuss risk factors for TDF nephrotoxicity and its implications for screening for renal disease in those patients with CHB monoinfection on TDF, and the use of TDF in at-risk populations.

KHA-CARI guideline: recipient assessment for transplantation.

Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Child & Adolescent Renal Service, Royal Children’s and Mater Children’s Hospitals, Brisbane, Queensland, Renal Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Department of Nephrology, Monash Medical Centre and Department of Medicine, Monash University, Melbourne, Victoria, and Renal Transplantation, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and Department of Renal Medicine, Auckland City Hospital and Department of Medicine, Auckland University, Auckland, New Zealand

Adult nephrotic syndrome: non-specific strategies for treatment.

SUMMARY:  Irrespective of aetiology, the nephrotic syndrome presents a range of potentially serious complications. These include thrombo‐embolism, infection and hyperlipidaemia. Despite the prevalence of the nephrotic state among renal patients, there has been little prospective analysis of the therapeutic approach to these potentially life‐threatening events even though their pathogenesis has been examined in some detail. Most of these complications are more prevalent once the albumin concentration falls below 20 g/L and it is recognized that restoration of serum albumin significantly diminishes their frequency. However, this may be difficult to achieve, especially in adults. The problems of thrombo‐embolism and infection are of immediate concern but, in persistent cases, the additional issues of hyperlipidaemia and loss of bone density also require consideration for therapy. Thus, in addition to specific attempts to reduce proteinuria, it is recommended that high‐risk nephrotic patients receive anticoagulation, pneumococcal vaccination and lipid lowering therapy. Strategies for the preservation of bone density should also be considered, particularly in patients who receive high‐dose corticosteroids. Among a range of non‐specific treatments for proteinuria, angiotensin‐converting enzyme inhibitors appear best in terms of efficacy and safety. Prospective trials are required to clarify the longitudinal impact of these generic strategies on the protection of the persistently nephrotic patient.

Screening and management of renal disease in human immunodeficiency virus-infected patients in Australia

Renal disease has become one of the most important comorbidities observed in the human immunodeficiency virus (HIV)‐infected patient cohort. Data are lacking on the current screening and management of renal disease in patients with HIV. We evaluated HIV‐infected Australian adults in primary care to determine current practices.

Outcomes of cardiac surgery in chronic kidney disease

OBJECTIVE To identify predictors of early and late outcomes of cardiac surgery in patients with chronic kidney disease. METHODS Patients (n=545) with serum creatinine≥200 μmol/L or renal dialysis were identified from databases maintained by the largest Sydney cardiothoracic surgical units with data consistent with the Australian and New Zealand Society of Cardiothoracic Surgeons data definitions. The patient data were matched against the National Dialysis Database and the New South Wales Register of Births, Deaths, and Marriages. Statistical analysis was used to identify predictors of early and late outcomes. RESULTS The Kaplan-Meier estimate of 1-, 5-, and 10-year survival for all patients was 78%, 56%, and 36%, respectively. The outcomes were similar after coronary bypass surgery and valve replacement and were also similar for dialysis and nondialysis patients. The odds ratios for the significant independent predictors of outcomes were, for perioperative death, age (1.4 per decade), emergency surgery (7.0), redo surgery (3.8), left ventricular impairment (moderate, 2.7; severe, 4.4); for new early postoperative dialysis, estimated glomerular filtration rate<20 mL/min (3.8), emergency surgery (2.7), tricuspid valve surgery (4.4); for new permanent dialysis within 6 months of surgery, serum estimated glomerular filtration rate<20 mL/min (odds ratio, 4.6). The hazard ratio for the independent predictors of late death in those alive 6 months after surgery was 1.4 per decade for age and 1.4 for moderate or severe left ventricular impairment. CONCLUSIONS Left ventricular impairment is a risk factor for perioperative and late death in patients with kidney disease. After cardiac surgery, preoperative dialysis-dependent and dialysis-free patients had similar long-term outcomes.

Screening and management of cardiovascular disease in Australian adults with HIV infection

BACKGROUND Cardiovascular disease (CVD) is common in HIV infection. With no specific Australian guidelines for the screening and management of CVD in HIV-infected patients, best clinical practice is based on data from the general population. We evaluated adherence to these recommendations by primary care physicians who treat HIV-infected patients. METHODS Primary care physicians with a special interest in HIV infection were asked to complete details for at least 10 consecutive patient encounters using structured online forms. This included management practices pertaining to blood pressure (BP), blood glucose, electrocardiogram, lipid profile and CVD risk calculations. We assessed overall adherence to screening and follow-up recommendations as suggested by national and international guidelines. RESULTS Between May 2009 and March 2010, 43 physicians from 25 centres completed reporting for 530 HIV-infected patients, of whom 93% were male, 25% were aged 41-50 years and 83% were treated with antiretrovirals. Risk factors for CVD were common and included smoking (38%), hyperlipidaemia (16%) and hypertension (28%). In men aged >40 years and women aged >50 years without evidence of ischaemic heart disease, only 14% received a CVD risk assessment. Lipid and BP assessments were performed in 87% and 88% of patients, respectively. CONCLUSIONS This Australian audit provides unique information on the characteristics and management of HIV and CVD in clinical practice. We have found a high burden of risk for CVD in HIV-infected Australians, but current screening and management practices in these patients fall short of contemporary guidelines.

Adult nephrotic syndrome: Non‐specific strategies for treatment (Review Article)

SUMMARY:  Irrespective of aetiology, the nephrotic syndrome presents a range of potentially serious complications. These include thrombo‐embolism, infection and hyperlipidaemia. Despite the prevalence of the nephrotic state among renal patients, there has been little prospective analysis of the therapeutic approach to these potentially life‐threatening events even though their pathogenesis has been examined in some detail. Most of these complications are more prevalent once the albumin concentration falls below 20 g/L and it is recognized that restoration of serum albumin significantly diminishes their frequency. However, this may be difficult to achieve, especially in adults. The problems of thrombo‐embolism and infection are of immediate concern but, in persistent cases, the additional issues of hyperlipidaemia and loss of bone density also require consideration for therapy. Thus, in addition to specific attempts to reduce proteinuria, it is recommended that high‐risk nephrotic patients receive anticoagulation, pneumococcal vaccination and lipid lowering therapy. Strategies for the preservation of bone density should also be considered, particularly in patients who receive high‐dose corticosteroids. Among a range of non‐specific treatments for proteinuria, angiotensin‐converting enzyme inhibitors appear best in terms of efficacy and safety. Prospective trials are required to clarify the longitudinal impact of these generic strategies on the protection of the persistently nephrotic patient.

Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database: CKD in Australian HIV-infected patients

The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV‐infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population.

Chronic kidney disease in Australian HIV-infected patients: analysis of the Australian HIV Observational Database

The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV‐infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population.

Rapid recovery of renal function after pulse steroid therapy in a human immunodeficiency virus-infected patient with glomerulonephritis

Renal disease is an important complication of human immunodeficiency virus (HIV) infection and its prevalence is increasing. HIV-specific renal lesions are well described and include HIV-associated nephropathy as well as HIV immune complex disease of the kidney and thrombotic microangiopathy. These HIV-associated lesions are seen less commonly in the era of highly active antiretroviral therapy (HAART), but still remain important in those patients with a late diagnosis of HIV, or those patients not on therapy. In the HAART era, toxicities from antiretroviral drugs and complications from noninfectious comorbidities have become more frequent causes of chronic kidney disease in this patient cohort. Concurrent primary kidney diseases are also seen with the increased survival of this patient cohort. Clinically, it is often difficult to distinguish these aetiologies in the absence of a renal biopsy. For the first time, we describe an HIV-infected patient with acute kidney injury secondary to anti-neutrophil cytoplasm antibody (ANCA)-negative pauci-immune mesangial proliferative glomerulonephritis on a background of acute tubular necrosis, with rapid response to treatment with steroid therapy. The absence of ANCA is unusual; ANCA are frequently found in the sera of HIVpositive patients, often in patients with no signs of vasculitis. ANCA-associated microscopic polyangiitis has previously been described in HIV-infected patients. A 63-year-old white man presented to the emergency department short of breath in September 2011. At presentation, he had acute respiratory distress, with a respiratory rate of 44 breaths per minute, and an oxygen saturation level of 66% on room air. He was afebrile with a normal blood pressure and had a pulse rate of 100 beats per minute. He had been diagnosed with HIV in 1987, but, because of the patient’s wishes, was treatment naïve. He was immunodeficient, with a CD4+ T-cell count of 0.08 ¥ 10/L and had a detectable HIV-RNA load of 190 470 copies/mL. The patient had previously been offered HAART but declined and instead was using multiple herbal preparations in its place. He also had hepatitis B with spontaneous clearance and renal impairment, which had not been investigated. In December 2010, his serum creatinine was 125 mmol/L; estimated glomerular filtration rate (eGFR) 54 mL/min/1.73 m. After resuscitation, he was admitted to the intensive care unit (ICU) and treated for proven Pneumocystis jiroveci pneumonia. He had acute kidney injury, presumed secondary to his acute illness. The creatinine on admission to ICU was 881 mmol/L; eGFR 6 mL/min/1.73 m. He required invasive ventilation and continuous venovenous haemodialysis and was commenced on sulphamethoxazole and trimethoprim. He remained in the ICU for 2 weeks and gradually improved. Upon renal review after discharge from ICU, he was dialysis dependent. Further investigations revealed dysmorphic microhaematuria and a 24-h protein excretion of 0.6 g. Renal ultrasound demonstrated normal-sized kidneys without obstruction. Autoantibodies against neutrophil cytoplasm, glomerular basement membrane and double-stranded DNA were negative, as was his antinuclear antibody. No cryoglobulins were detected in the serum. The serum electrophoresis and complement levels were normal. Hepatitis B virus (HBV)-DNA and hepatitis B surface antigen were not detected, nor was hepatitis C antibody. A renal biopsy was performed (Fig. 1). Histologically, the primary diagnosis was pauciimmune mesangial proliferative glomerulonephritis with crescents in 30% of glomeruli sampled. There were no immune deposits on electron microscopy and the immunofluorescence was negative. In addition, the tubules demonstrated degenerative changes consistent with acute tubular necrosis. Despite concerns regarding the use of immunosuppressive treatment in a profoundly immunodeficient patient, therapy with intravenous bolus methylprednisolone (500 mg daily) was commenced to test for reversibility of the glomerular lesion. After 3 days, the patient was converted to oral prednisone therapy (1 mg/kg). He was placed on prophylaxis against other infective complications with azithromycin, valacyclovir and fluconazole. There was a rapid improvement in renal function (Fig. 1c). At review in December 2011, his creatinine was 124 mmol/L; eGFR 54 mL/min/1.73 m. The patient has also commenced abacavir, lamivudine and nevirapine, agents chosen to avoid renal toxicity. He continues on prophylactic dose sulphamethoxazole and trimethoprim. The broad spectrum of renal diseases seen in HIVinfected patients often results in difficultly in making an accurate diagnosis in the absence of a renal biopsy. This bs_bs_banner