Increase in nephrology advanced trainee numbers in Australia and associated reduction in clinical exposure over the past decade.

BACKGROUND: Advanced training in nephrology should provide broad experience in all aspects of nephrology. In Australia, the Specialist Advisory Committee in Nephrology oversees nephrology training, and recent increases in advanced trainee numbers have led to concern about dilution of training experience. No study has examined variations in clinical exposure for nephrology trainees in Australia. AIM: To assess the changes in nephrology advanced training in Australia with respect to trainee numbers and exposure to patients and procedures over the past 10 years. METHODS: A retrospective study was performed by obtaining all available Royal Australasian College of Physician supervisor reports from 2000 to 2010 to determine differences in clinical exposure and procedures performed by nephrology trainees. RESULTS: Five hundred and forty-two reports were reviewed involving 208 nephrology trainees in Australia across 53 different training sites. In 2000, 22 trainees were undertaking a core clinical year of training. Trainee numbers have steadily risen from 33 in 2004 to 84 in 2010. The greatest increases have occurred in New South Wales, Victoria and Queensland (sixfold, threefold and fivefold increases respectively). Trainee exposure to dialysis patients has gradually decreased in the past decade. The average number per trainee per year in 2000 compared with 2010 were 66 versus 43 (P = 0.02) and 28 versus 16 (P = 0.01) for haemodialysis and peritoneal dialysis respectively. Acute kidney injury cases per trainee showed a gradual nonsignificant reduction over time and average procedural numbers per trainee decreased significantly from 2000 to 2010 with fewer temporary dialysis catheters inserted per year (39 vs 10, P < 0.01) and fewer renal biopsies performed per year (65 vs 41, P < 0.01). The proportion of trainees working in a hospital that does not provide exposure to acute transplantation has steadily increased from 15% in 2003 to 44% in 2010. CONCLUSIONS: There has been a dramatic and significant increase in nephrology advanced trainee numbers over the past decade at a more rapid rate than the growth in dialysis and transplant patient numbers. This study suggests that training experience has diminished over the past decade and supports a 3-year core clinical nephrology training programme in Australia.

Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression.

Patients with kidney failure are at high risk of a cardiac death and frequently develop left ventricular hypertrophy (LVH). The mechanisms involved in the cardiac structural changes that occur in kidney failure are yet to be fully delineated. Angiotensin-converting enzyme (ACE) 2 is a newly described enzyme that is expressed in the heart and plays an important role in cardiac function. This study assessed whether ACE2 plays a role in the cardiac remodelling that occurs in experimental acute kidney injury (AKI). Sprague-Dawley rats had sham (control) or subtotal nephrectomy surgery (STNx). Control rats received vehicle (n = 10), and STNx rats received the ACE inhibitor (ACEi) ramipril, 1 mg kg(-1) day(-1) (n = 15) or vehicle (n = 13) orally for 10 days after surgery. Rats with AKI had polyuria (P < 0.001), proteinuria (P < 0.001) and hypertension (P < 0.001). Cardiac structural changes were present and characterized by LVH (P < 0.001), fibrosis (P < 0.001) and increased cardiac brain natriuretic peptide (BNP) mRNA (P < 0.01). These changes occurred in association with a significant increase in cardiac ACE2 gene expression (P < 0.01) and ACE2 activity (P < 0.05). Ramipril decreased blood pressure (P < 0.001), LVH (P < 0.001), fibrosis (P < 0.01) and BNP mRNA (P < 0.01). These changes occurred in association with inhibition of cardiac ACE (P < 0.05) and a reduction in cardiac ACE2 activity (P < 0.01). These data suggest that AKI, even at 10 days, promotes cardiac injury that is characterized by hypertrophy, fibrosis and increased cardiac ACE2. Angiotensin-converting enzyme 2, by promoting the production of the antifibrotic peptide angiotensin(1-7), may have a cardioprotective role in AKI, particularly since amelioration of adverse cardiac effects with ACE inhibition was associated with normalization of cardiac ACE2 activity.

Heparanase in glomerular diseases.

Heparanase is an endo-beta(1-4)-D-glucuronidase that degrades heparan sulfate (HS) polysaccharide side chains. The role of heparanase in metastasis, angiogenesis, and inflammation has been established. Recent data suggest a role for heparanase in several proteinuric diseases and an increased glomerular heparanase expression is associated with loss of HS in the glomerular basement membrane (GBM). Furthermore, an increase in heparanase activity was detected in urine from proteinuric patients. Mice with transgenic heparanase overexpression developed mild proteinuria. Glomerular heparanase activity is proposed to lead to loss of HS in the GBM and proteinuria. Because the primary role of GBM HS for charge-selective permeability has been questioned recently, heparanase may induce or enhance proteinuria by (i) changes in the glomerular cell-GBM interactions, due to loss of HS; (ii) release of HS-bound factors and HS fragments in glomeruli; or (iii) intracellular signaling by binding of heparanase to glomerular cells. Which of these mechanisms is prevailing requires further research. The precise mechanisms leading to increased heparanase expression in the different glomerular cell types remain elusive, but may involve hyperglycemia, angiotensin II, aldosterone, and reactive oxygen species. This review focuses on the role of heparanase in HS degradation in proteinuric diseases and the possibility/feasibility of heparanase inhibitors, such as heparin(oids), as treatment options.

Quinine-induced renal failure as a result of rhabdomyolysis, haemolytic uraemic syndrome and disseminated intravascular coagulation.

This report describes a case of quinine-induced acute renal failure as a result of a combination of haemolytic uraemic syndrome and rhabdomyolysis with disseminated intravascular coagulation. The abrupt onset of symptoms occurred after ingestion of 300 mg of quinine along with atorvastatin. The patient recovered with supportive management, suggesting that plasma exchange may not be necessary in this situation. The possibility of a drug interaction contributing to rhabdomyolysis is raised. The proposed mechanism is through quinine inhibition of the cytochrome P450 isoenzyme 3A4, which may increase systemic levels of atorvastatin by reducing its first-pass metabolism.

Increased expression of heparanase in puromycin aminonucleoside nephrosis.

BACKGROUND: The beta-D-endoglycosidase heparanase has been proposed as an important contributor to loss of glomerular charge in proteinuria. Expression of heparanase was, therefore, determined in acute puromycin aminonucleoside (PAN) nephrosis. METHODS: A rabbit polyclonal antibody was produced against a 17-amino acid peptide derived from the predicted amino acid sequence of heparanase. The antibody was validated by Western blot. Immunohistochemical staining and Western blotting were used to localize heparanase protein in normal kidneys and kidneys from rats with PAN nephrosis. Northern blot analysis was used to determine mRNA expression. RESULTS: Immunohistochemical staining showed that heparanase protein was localized to tubular cells in the distal convoluted tubules, thick ascending limb of the loop of Henle, and transitional cell epithelium in normal kidney. Minimal expression was noted in normal glomeruli. Western blot analysis of protein from isolated normal glomeruli showed minimal expression of the 65 kD proheparanase protein. A marked increase in the staining for heparanase was found at day 5 of the PAN nephrosis model, at approximately the time of onset of proteinuria, and at day 14. Expression was predominantly seen in podocytes. At day 5, only the 65 kD proheparanase species was identified, but at day 14, mature 58 kD heparanase also was present. Northern blot analysis of sieved glomeruli at day 14 confirmed an increase in heparanase mRNA. The human podocyte cell line 56/10A1 also produced both proheparanase and mature heparanase, suggesting that podocytes can activate heparanase without other cell types. CONCLUSION: The previously mentioned data confirm that the novel beta-D-endoglycosidase heparanase is up-regulated and activated in glomeruli from rats with proteinuria. Heparanase may be involved, therefore, in the loss of glomerular charge seen in proteinuria. Moreover, the presence of heparanase in normal tubules suggests that it may also be involved in cell migration or turnover.