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Background Off-label use of rituximab in lupus nephritis is reported to be beneficial. While the optimal dose is unknown, the regimen of four intravenous doses of 375 mg/m(2) is commonly employed, despite expense and potential side-effects. Aim To investigate the response to single-dose rituximab, added to standard corticosteroids plus additional immunosuppressive agent, in refractory lupus nephritis. Methods Consecutive consenting patients with refractory lupus nephritis despite steroids plus either cyclophosphamide, mycophenolate or azathioprine were enrolled in this ethics-approved, open-label, prospective study. After baseline assessment, patients received one intravenous infusion of 375 mg/m(2) rituximab. Clinical, biochemical and serological (DsDNA, complement) responses to this dose were analysed. Complete renal response (CR) was defined as normalisation of creatinine, albumin, proteinuria and urinary RBCs and partial response (PR) as ≥50% improvement in at least one parameter, without deterioration in others. B-cell depletion was defined as peripheral CD19 lymphocyte count ≤0.05 × 10(9) /L. Results Fourteen patients were enrolled in the study. All were B-cell-depleted until 8 months post-dose. Eleven patients (79%) responded (2CR, 9PR) at a median time of 5 months, with a 6-month probability of renal response of 43%. Five patients (45%) relapsed at a median time of 17 months. DsDNA titres decreased in 69%. Side-effects were minimal. Conclusions Single-dose rituximab is effective in relapsed/refractory lupus nephritis. Longevity of B-cell depletion with single-dose rituximab is similar to that of four doses with potentially fewer side-effects.

Aim: Vascular calcification is prevalent in patients with chronic kidney disease. Abdominal aortic calcification (AAC) can be detected by X-ray, although AAC is less well documented in anatomical distribution and severity compared with coronary calcification. Using simple radiological imaging we aimed to assess AAC and determine associations in prevalent Australian haemodialysis (HD) patients. Methods: Lateral lumbar X-ray of the abdominal aorta was used to determine AAC, which is related to the severity of calcific deposits at lumbar vertebral segments L1 to L4. Two radiologists determined AAC scores, by semi-quantitative measurement using a validated 24-point scale, on HD patients from seven satellite dialysis centres. Regression analysis was used to determine associations between AAC and patient characteristics. Results: Lateral lumbar X-ray was obtained in 132 patients. Median age of patients was 69 years (range 29–90), 60% were male, 36% diabetic, median duration of HD 38 months (range 6–230). Calcification (AAC score ≥ 1) was present in 94.4% with mean AAC score 11.0 ± 6.4 (median 12). Independent predictors for the presence and severity of calcification were age (P = 0.03), duration of dialysis (P = 0.04) and a history of cardiovascular disease (P = 0.009). There was no significant association between AAC and the presence of diabetes or time-averaged serum markers of mineral metabolism, lipid status and C-reactive protein. Conclusions: AAC detected by lateral lumbar X-ray is highly prevalent in our cohort of Australian HD patients and is associated with cardiovascular disease, increasing age and duration of HD. This semi-quantitative method of determining vascular calcification is widely available and inexpensive and may assist cardiovascular risk stratification.

Background: The clinical impression of Australian physicians is that systemic lupus erythematosus (SLE) is more prevalent and more severe in Asian patients than in their Caucasian counterparts. The presence and severity of lupus nephritis is a major determinant of prognosis in SLE, and largely determines disease impact. Aim: To analyse the relationships between ethnicity and the prevalence and severity of lupus nephritis (LN) in patients attending a tertiary referral centre (The Royal Melbourne Hospital (RMH)). Methods: The ethnicity of all known patients with biopsy-proven LN was determined according to three definitions of ethnicity – ancestry, country of origin and primary language spoken. The prevalence of Asian ethnicity in the LN cohort was analysed across severity class, and was compared with the prevalences of Asian ethnicity in the general population within the hospital's geographic area, and with that in the relevant RMH cohorts of inpatients and outpatients, over the same time period. Results: Within this single tertiary centre, Asian patients were disproportionately represented in both the systemic lupus erythematosus (SLE) and the LN patient groups, although the distribution of histological severity of LN was not significantly different from Caucasian patients. Conclusion: This study supports the common clinical impression that SLE is more common and more severe in the Asian-Australian population. Asian patients with SLE were more commonly diagnosed with LN. However, the spectrum of histological severity of LN was similar in Asian and Caucasian patients.

Thrombotic thrombocytopenic purpura is a rare condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, altered neurology, renal impairment and fever. While plasma exchange has reduced mortality from more than 90% to between 10 and 30%, a proportion of cases fail to respond. Rituximab may be efficacious in the management of refractory cases of thrombotic thrombocytopenic purpura. We present two cases in which rituximab was used with successful outcomes. Treatment resulted in resolution of severe clinical and haematological abnormalities in both patients. There has been no relapse after 16 months follow up. Our experience supports the use of rituximab in difficult cases of TTP. Ongoing evaluation of its use is in progress at our institution.

SUMMARY: Background: Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin (Hb) concentration when patients are switched from a subcutaneous (SC) to intravenous (IV) route of administration. Many of the reported trials, however, involved patients who did not have adequate serum iron levels. It was hypothesized that patients with adequate iron stores who are switched from one route of administration to the other without a change in dose will experience substantially less change in their Hb concentration. Methods: Haemodialysis patients who were iron replete (ferritin 300–800 µg/L, transferrin saturation (TSAT) 25–50%) participated in a prospective, randomized cross-over trial receiving epoetin for 3 months either by SC or IV injection followed by a further 3 months of epoetin via the other route. The principal aim was to determine changes in Hb concentration without altering the weekly epoetin dose. The secondary aim was to assess whether the frequency of dosing (once, twice or thrice weekly) influenced the Hb concentration response. Results: Eighty-one patients (mean age 62 years, 60% male) entered the study and 15 withdrew prior to study completion. Forty-three patients began SC epoetin alfa administration (group A) and 38 on IV (group B). Median ferritin and TSAT at entry for groups A and B were 409 and 394 µg/L (NS) and 31 and 32% (NS), respectively, which remained within the target range during the study. Median epoetin doses for groups A and B were similar (90 vs 93 IU/kg per week, NS). After 3 months, the mean Hb concentration rose for group A (SC; 118.7–121.9 g/L (P = 0.03)) but it fell for group B (IV; 119.1–116.0 g/L (P = 0.019)). Following the change in route of administration, the Hb concentration for group A (IV) fell by 5.1% over 3 months (121.9–115.4, P

SUMMARY: Screening patients with autosomal dominant polycystic kidney disease (ADPKD) for asymptomatic intracranial aneurysms has been proposed as a method of reducing the morbidity and mortality associated with aneurysm rupture. However, recent studies have shown lower spontaneous rupture rates of small aneurysms and higher risks of significant complications with interventions than previously reported. Risk-benefit analysis has not demonstrated any benefit of screening ADPKD patients without a history of subarachnoid haemorrhage (SAH) for intracranial aneurysms, and has suggested that screening might cause harm.

We describe three cases of acute renal failure in young men who ingested wild mushrooms with the intent of producing hallucinations. Two cases remained dialysis dependent and, in these cases, renal biopsy revealed tubulointerstitial nephritis and fibrosis. Similar cases have been reported in other countries, but not in Australia. The most recognized mushroom nephrotoxin is orellanine, however the causative mushroom species and the actual toxin involved in these cases are unknown.

Orthotopic liver transplantation is used for treatment of liver cirrhosis and organ failure due to chronic hepatitis B infection. However, in the absence of effective antiviral therapy, patients can develop recurrent hepatitis B leading to graft failure. In this report, a review is presented of several European studies that have demonstrated the efficacy of hepatitis B immunoglobulin (HBIg) in lowering the rate of recurrence or the severity of the recurrent infection. Clinical protocols and results of these studies are described in detail. Several important conclusions can be derived from the clinical results. HBIg is most effective when administered in high doses for a long time. Characteristics of the recipients, such as the presence or absence of viral DNA, can also affect the rate of recurrence. Intramuscular injection of HBIg has minimal side effects and results in reduced cost relative to intravenous injection.

SUMMARY: The kinetics of interstitial extracellular matrix remodelling in the kidney following parenchymal cell death were studied after injury was produced by a single application of liquid nitrogen to the surface of the kidney. the size of the injury decreased to 30% of the original size at 4 days and to 5% at 16 days after injury. the primary response to injury consisted of an acute polymorphonuclear infiltration followed by monocyte/macrophage and myofibroblast accumulation from day 2 to 8. Collagen III accumulation increased progressively until day 16 and was inversely related to lesion size. These results demonstrate the time course of cellular events and collagen synthesis in renal tissue remodelling following renal parenchymal cell death.

Summary: Interstitial fibrosis is a final common pathway for many, if not all forms of end-stage renal disease. Although the kidney contains several cell types that are capable of collagen biosynthesis, most in vitro and in vivo studies suggest that fibroblasts generate the principal interstitial matrix collagens. Recent studies have defined a role for myofibroblasts (cells with features of both fibroblasts and smooth muscle cells) in progressive renal interstitial fibrosis. Renal myofibroblasts are hyperproliferative and up-regulated matrix producers, consistent with them being ‘activated’ fibroblasts. Interstitial myofibroblasts also share a number of anatomical, phenotypic and biosynthetic features with the glomerular mesangial cell. the interstitium consists of a complex mixture of inflammatory and fibrogenic mediators. the fibroblast response to this microenvironment includes chemotaxis, proliferation and increased synthetic activity. However, the derivation and fate of the fibroblast/myofibroblast during scarring remains unclear, with migration, proliferation, differentiation and cell death all likely to determine cell number.

Summary: Resolution of tubulointerstitial nephritis represents an important step in limiting renal fibrogenesis. However, the mechanism of this resolution remains poorly understood. to determine if apoptosis has a role in this process, we studied its incidence in an experimental model of renal infection and scarring, induced by direct inoculation of Escherichia coli into the renal cortex of Sprague-Dawley rats. the focal lesion produced was studied in animals killed at various time points up to 100 days post inoculation. Apoptosis was identified by electron microscopy (EM) and in-situ labelling of fragmented DNA using terminal transferasemediated deoxy-uridine-5′-triphospate (UTP) nick end labelling (TUNEL). Results were compared with morphological assessment of tubulointerstitial cellularity and macrophage localization. Terminal transferasemediated UTP nick end labelling localized apoptosis to interstitial cells, tubular casts and occasional tubular epithelia and double labelling demonstrated apoptotic body incorporation in macrophages. Interstitial cellularity was maximum at day 3, decreasing significantly by 100 days (P< 0.01). the incidence of interstitial apoptosis was increased by 3 days and remained significantly higher than day 0 controls throughout (P < 0.05). Tubular cellularity was significantly less than in control animals throughout the experimental time period. Although the rate of tubular apoptosis was increased, this difference was not statistically significant. In conclusion, apoptosis may represent an important mechanism in the reduction of tubulointerstitial cellularity after experimental renal infection. This in turn, may be important in limiting subsequent interstitial scarring.

Summary: Confocal laser scanning microscopy (CLSM) has potential applications in the fields of embryology, anatomy, physiology and pathology of the kidney. This review focuses upon the principles of confocal microscopy and the ways in which this new technology may affect nephrological diagnostic pathology.

Summary: Future studies aimed at testing therapies to prevent progression of renal failure have much to learn from the past successful and unsuccessful attempts. Given the insensitivity of all other methods, the proper index of renal function for study of progression of renal failure should be radioisotope glomerular filtration marker clearance. Randomized prospective controlled studies are required, and statistical analysis should be designed to allow consideration for patient drop out and covariants. Since compensatory mechanisms come into place as soon as there is any nephron damage, more attention should be paid to studying the progression of renal failure from a normal glomerular filtration rate (GFR) until there is an elevated plasma creatinine level. This suggestion is supported by four under-lying concepts: (i) overall GFR does not fall until about 23% of nephrons are destroyed; (ii) if progression is multifactorial, the later in the progress the more likely that more factors are present to confound issues; (iii) this may allow study of greater patient numbers, since patients who have had renal biopsy or ultrasound diagnosis can be entered before the plasma creatinine is abnormal; (iv) in early stages of disease, issues of concurrent treatment may be less difficult (e.g. diet, phosphate control, hypertension). With diabetes, prognosis and progression has been related to proteinuria. In non-diabetic disease proteinuria has been related to progression, but the effect of alleviation of proteinuria on prognosis has not been intensively studied. There is a need to study the relationships between proteinuria and progression, particularly in early renal disease. At present most therapies are based upon observations in the partially ablated rat model. Other animal models should be developed, and the details of early mechanisms in the rat further clarified. Since we believe progression is likely to be multifactorial in pathogenesis, combination therapies may be required to optimally reduce progression.

AFCKDI RECOMMENDATIONS FOR EARLY DETECTION OF CHRONIC KIDNEY DISEASE 1. Targets Patients with diabetes, hypertension Those with family history of chronic kidney disease (CKD) Individuals receiving potentially nephrotoxic drugs, herbs or substances or taking indigenous medicine Patients with past history of acute kidney injury Individuals older than 65 years 2. Tools Spot urine sample for protein with standard urine Dipstick test (need a repeat confirmatory test if positive) Dipstick for red blood cells (need confirmation by urine microscopy) An estimate of glomerular filtration rate based on serum creatinine concentration 3. Frequency of screening Screening frequency for targeted individuals should be yearly if no abnormality is detected on initial evaluation. 4. Who should perform the screening Doctors, nurses, paramedical staff and other trained healthcare professionals 5. Intervention after screening Patients detected to have CKD should be referred to primary care physicians with experience in management of kidney disease for follow up. A management protocol should be provided to the primary care physicians. Further referral to nephrologists for management will be based on the protocol together with clinical judgment of the primary care physicians with their assessment of the severity of CKD and the likelihood of progression. 6. Screening for cardiovascular disease risk It is recommended that cardiovascular disease risk factors should be screened in all patients with CKD.