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Background Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials.Methods In this meta-analysis, we searched PubMed for publications in English from Jan 1, 1946, to Dec 15, 2016, using search terms including "chronic kidney disease", "chronic renal insufficiency", "albuminuria", "proteinuria", and "randomized controlled trial"; key inclusion criteria were quantifiable measurements of albuminuria or proteinuria at baseline and within 12 months of follow-up and information on the incidence of end-stage kidney disease. We requested use of individual patient data from the authors of eligible studies. For all studies that the authors agreed to participate and that had sufficient data, we estimated treatment effects on 6-month change in albuminuria and the composite clinical endpoint of treated end-stage kidney disease, estimated glomerular filtration rate of less than 15 mL/min per 1.73 m(2), or doubling of serum creatinine. We used a Bayesian mixed-effects meta-regression analysis to relate the treatment effects on albuminuria to those on the clinical endpoint across studies and developed a prediction model for the treatment effect on the clinical endpoint on the basis of the treatment effect on albuminuria.Findings We identified 41 eligible treatment comparisons from randomised trials (referred to as studies) that provided sufficient patient-level data on 29 979 participants (21 206 [71%] with diabetes). Over a median follow-up of 3.4 years (IQR 2.3-4.2), 3935 (13%) participants reached the composite clinical endpoint. Across all studies, with a meta-regression slope of 0.89 (95% Bayesian credible interval [BCI] 0.13-1.70), each 30% decrease in geometric mean albuminuria by the treatment relative to the control was associated with an average 27% lower hazard for the clinical endpoint (95% BCI 5-45%; median R-2 0.47, 95% BCI 0.02-0.96). The association strengthened after restricting analyses to patients with baseline albuminuria of more than 30 mg/g (ie, 3.4 mg/mmol; R-2 0.72, 0.05-0.99]). For future trials, the model predicts that treatments that decrease the geometric mean albuminuria to 0.7 (ie, 30% decrease in albuminuria) relative to the control will provide an average hazard ratio (HR) for the clinical endpoint of 0.68, and 95% of sufficiently large studies would have HRs between 0.47 and 0.95.Interpretation Our results support a role for change in albuminuria as a surrogate endpoint for the progression of chronic kidney disease, particularly in patients with high baseline albuminuria; for patients with low baseline levels of albuminuria this association is less certain. Copyright (c) 2019 Elsevier Ltd. All rights reserved.

Sepsis is a common medical condition resulting from an infectious stimulus with a variable inflammatory response leading to a spectrum of clinical conditions from mild constitutional symptoms to varying degrees of organ dysfunction and death. The understanding of the patho-physiology of sepsis has lead to better treatment modalities and whilst sepsis is an increasingly more common condition world wide, the mortality from sepsis is nevertheless falling. Treatment algorithms have been promulgated over the years and levels of evidence for these have varied. This review will focus on the early management issues recently updated and released by a multi-national panel of experts based on best evidence, aimed at reducing sepsis related mortality by 25%.

This review will address the issue that renal dysfunction post cardiac surgery, whether pre-existent or developing de novo, is a major contributor to morbidity as well as short- and long-term survival. The ability to recognise diminished renal reserve through estimating glomerular filtration rate, makes clinicians more vigilant to protecting renal function through better haemodynamic post-operative management and avoidance of nephrotoxins. Further the application of the recent consensus classification of acute renal dysfunction allows early recognition of renal impairment and earlier intervention with renal replacement therapy. This early renal replacement therapy has been shown to lead to better outcome.

Mechanical circulatory support has evolved markedly over recent years. ECMO (extra corporeal membrane oxygenation) is instituted for the management of life threatening pulmonary or cardiac failure (or both), when no other form of treatment has been or is likely to be successful. Most commonly, it is instituted in an emergency or urgent situation after failure of other treatment modalities. It is used as temporary support, usually awaiting recovery of organs, or can be used as a bridge to a more permanent device or cardiac transplantation. ECMO can be deployed in a veno-arterial configuration (either peripheral or central cannulation) for the treatment of cardiogenic shock. This is usually seen post-cardiotomy, post-heart transplant and in severe cardiac failure due to almost any other cause (e.g. cardiomyopathy, myocarditis, acute coronary syndrome with cardiogenic shock). Veno-venous ECMO is used for respiratory failure and usually involves peripheral cannulation using the femoral veins+/-internal jugular vein if required. The indications for veno-venous ECMO are respiratory failure, most commonly due to adult respiratory distress syndrome (ARDS), pneumonia, trauma or primary graft failure following lung transplantation. ECMO is also used for neonatal and paediatric respiratory support. Its use in premature neonates is the mainstay of treatment for immature lungs and insufficient surfactant. In this review, the technical aspects of ECMO cannulation, maintenance and weaning are outlined. Complication rates and outcomes are reviewed and our experience at The Epworth Hospital is summarized.

Recombinant factor VII was first developed for control and prevention of bleeding in haemophilia with antibodies to factor VIII and IX. Its efficacy in these situations is well established. Over recent years, the ‘off-label’ use of this substance has become more widespread in trauma, surgery and obstetric bleeding. Here we describe the mechanism of action of recombinant factor VII, review current literature of ‘off-label’ usage and our initial experience in surgical related cases of bleeding at Epworth Hospital.

Background: The purpose of the present paper was to assess the performance of the European system for cardiac operative risk evaluation (EuroSCORE) model in an Australian adult cardiac surgical population. Methods: The additive and logistic EuroSCORE models were retrospectively applied to predict operative mortality in 2106 consecutive patients undergoing cardiac surgery at St Vincent's Hospital, Melbourne between June 2001 and August 2003, and at Geelong Hospital between June 2001 and April 2004. The entire cohort and a subset of patients undergoing isolated coronary artery bypass graft (CABG) surgery were analysed. Model discrimination and calibration was tested by determining the area under the receiver operating characteristic (ROC) curve and Hosmer−Lemeshow χ2, respectively. Results: There were significant differences in the prevalence of risk factors between the Australian and European cardiac surgical populations. There were 81 deaths (observed mortality 3.85%) in the entire cohort and 39 deaths in the isolated CABG group (observed mortality 2.60%). The EuroSCORE models overestimated mortality (entire cohort: additive predicted 5.75%, logistic predicted 9.93%; isolated CABG: additive predicted 4.87%, logistic predicted 7.71%). Discriminative power was very good for the entire cohort (area under ROC curve, 0.81 (additive) and 0.82 (logistic)). Calibration of both models was poor. Conclusion: The additive and logistic EuroSCORE model of risk prediction was not validated in the present population of cardiac surgical patients. The models may not accurately predict outcomes of patients undergoing cardiac surgery in Australia.

An 85-year-old woman presented to our emergency department 2 hours after a tiger snake (figure 1) bite to her hand. Within 30 minutes of arrival her conscious state rapidly deteriorated, and …

Background Although folate deficiency is common in pregnancy, progression to megaloblastosis is not. Hemolytic anemia, thrombocytopenia, and coagulopathy due to folate deficiency may mimic the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Cases Two women presented in the second trimester with abdominal pain and severe thrombocytopenia. These symptoms were misinterpreted in the first woman as the HELLP syndrome, leading to an emergency cesarean delivery. Subsequent investigation revealed folate deficiency; treatment resulted in rapid normalization of all abnormalities. In the second woman, folate deficiency was diagnosed antenatally. Treatment allowed continuation of the pregnancy to term. Conclusion The serious complications of folate deficiency make a strong case for supplementation in pregnancy. Careful scrutiny of clinical and laboratory findings may help discriminate the HELLP syndrome from its mimics, avoiding preterm delivery.

Metastatic bacterial endophthalmitis is a rare but devastating complication of septicaemia. We present 3 recent cases occurring in dialysis patients. Septicaemic dialysis patients seem particularly prone to staphylococcal endophthalmitis which developed in the face of therapeutic serum concentrations of appropriate antibiotics in all 3 cases. Prompt treatment, including consideration of intravitreal antibiotics, is required if vision is to be preserved. Early signs of endophthalmitis should be actively sought in septicaemic dialysis patients, as they are easily overlooked.

Mechanisms of progression of chronic renal failure (CRF) have been well documented in the rat but may not be relevant in man. Factors which may modify clinical CRF include underlying disease, diet, hypertension, intercurrent events, and adverse or beneficial effects of drug therapy. It has been argued that progression in many forms of renal disease is inexorable below a certain level of renal function. In other diseases, eg primary malignant hypertension, analgesic nephropathy, function frequently improves in both the short and long term with appropriate management. Thus knowledge of the nature of the underlying disease is essential in assessing progression. The value of diet in preserving renal function has been debated, particularly the relative roles of protein and phosphate control. In our own unit, a prospective randomized study showed a benefit of protein restriction. Development of accelerated hypertension is an important cause of progression of renal disease and clinical and experimental evidence supports the view that non-accelerated hypertension is also a factor in progression, amenable to treatment. Various intercurrent events may accelerate progression and function may be lost permanently following sepsis, urinary tract obstruction, renal arterial or venous obstruction, hypotension and in some cases pregnancy. Numerous drugs can have deleterious effects on the kidney. The possibility that converting enzyme inhibitors might preserve renal function is attracting attention but in view of their side effects their place in therapy should be determined by prospective controlled studies in which the above factors are carefully considered.

We evaluated the effects of ischemic renal failure (ATN) due to preservation and of prophylactic irradiation on renal transplant graft survival. Both ATN and prophylactic irradiation decreased actuari

This paper reports the only 6 cases of ureteric obstruction apparently caused by the gravid uterus diagnosed at the Mercy Maternity Hospital in the past 17 years, during which time there were 82,836 confinements. In 3 of the 6 cases there was clear radiographic evidence that the level of obstruction was at the pelvic brim. The rapid resolution of the ureteric obstruction shortly after delivery strongly suggested that the gravid uterus was the cause of the obstruction. Cases 1-3 were the only patients of 793 with polyhydramnios who developed bilateral ureteric obstruction and acute renal failure. In Cases 4 and 5 there was unilateral ureteric obstruction and pyelonephritis; in Case 4 a ureteric catheter was inserted from below, and in Case 5 a ureteric stent was inserted via a nephrostomy tube. In Case 6 a percutaneous nephrostomy tube was inserted.

During a 10 year study of women with reflux nephropathy 20 women had plasma creatinine concentrations in the range 0.2-0.4 mmol/l (2.3-4.5 mg/100 ml). Six experienced pregnancies exceeding 12 weeks' gestation. Pregnancy was associated with rapid deterioration in function in all six, resulting in end stage renal failure in four women within two years after delivery despite adequate control of blood pressure. Of the 14 women who did not have a prolonged pregnancy, four had periods of uncontrolled hypertension, all of which were related to non-compliance or loss from follow up, or both. Uncontrolled hypertension was also associated with accelerated renal failure, and all four women progressed quickly to end stage renal failure. The remaining 10 women were observed for from five to 10 years; in all 10 renal function deteriorated slowly, and none reached end stage renal failure within seven years. It is concluded that pregnancy in patients with reflux nephropathy and moderately severe renal failure has a deleterious effect on renal function.

Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure.

We assessed the effects of preservation on subsequent graft function by measuring and comparing creatinine and fractional protein clearances in 18 live-related (LR) and 38 cadaver-donor (CD) grafts, the latter selected on the basis of short warm ischemia times (less than 5 mins) and stable donor hemodynamic status prior to organ recovery. CD recipients with immediate graft function had lower initial creatinine clearances and greater fractional protein clearances than LR recipients. The role of preservation in producing greater fractional protein clearance was suggested by the observation of time-dependent increasing proteinuria during continuous hypothermic perfusion of four human CD kidneys and the significant correlation between the initial degree of proteinuria at onset of diuresis and the duration of cold preservation of those CD kidneys with immediate function. One-half of CD grafts, however, manifested acute renal failure (ARF) after implantation and in these grafts no correlation between cold preservation duration and fractional protein clearance at onset of diuresis was noted. Development of ARF in CD grafts was associated with still lower creatinine clearances, but higher fractional protein clearances during the first week of diuresis. These effects of preservation and those of preceding ARF on fractional protein clearances were no longer noted 2 wk after onset of diuresis in nonrejecting CD grafts. These observations suggest the presence of preservation-induced injury to grafts even when "immediate function" occurs.

A chemical, aurine tricarboxylic acid was used to identify aluminum in bone in a group of chronic renal failure patients with severe osteomalacia. Thirteen out of 49 (26%) patients had a positive stain at the bone-osteoid junction. The presence of aluminum at the staining site was confirmed by electron dispersion x-ray analysis. The patients' biopsies staining negative with this chemical, although having high bone aluminum levels, had more significant features of hyperparathyroidism, both biochemically and histologically than those having a positive stain. The usefulness of this technique to diagnose presymptomatic aluminum related osteomalacia is emphasized.

A slight modification in tissue processing and staining technique enables a previously described method for staining aluminium to be used to demonstrate aluminium in osteomalacia associated with haemodialysis. The stain appears to be accurate in diagnosing this condition and may assist in establishing the diagnosis before severe osteomalacia develops.

We measured prospectively changes in fractional protein clearance ratio (CPr/CCr) in 21 live-related (LR) and 41 cadaver donor (CD) renal transplants before and during onset of first rejections. Fifty-three recipients manifested a rejection within the first post-transplant month. Fractional protein clearance increased in all patients during rejection. An increase in CPr/CCr prior to other evidence of impending rejection, and therefore clinically useful, required at least a 10-day rejection-free interval dated from onset of diuresis (whether diuresis was immediate or delayed by acute tubular necrosis (ATN)). Twenty-three of 25 nonantilymphocyte globulin (ALG)-treated CD transplants manifested clinical and laboratory signs of the first rejection episode prior to the 10th day of diuresis compared with 5 of 21 LR and none of 16 ALG-treated CD transplants. Persistence of elevated CPr/CCr despite treatment forecast graft loss (11 of 13), whereas a decrease in this ratio was associated with ultimate reversal of the rejection process.

Renal osteodystrophy, in part due to secondary hyperparathyroidism, is one of the major unresolved problems affecting patients on chronic hemodialysis. In addition, evidence has shown that parathyroid hormone (PTH) is toxic to other organ systems besides bone. The results of a prospective study on the effect of propranolol in reducing PTH levels in chronic renal failure patients on hemodialysis are reported. Propranolol administration reduced PTH levels by over 50–75%. The levels of calcium, phosphorus, alkaline phosphatase and hematocrit were variable, but patients with severe derangements in these measurements also seemed to benefit from propranolol. It should now be determined by larger and longer studies whether these biochemical improvements can be translated into clinical benefits.

To examine the effect of pre-existing hypertension en pregnancy outcome, the clinical courses of 105 pregnancies undertaken by 76 wemen (55 normotensive, 21 hypertensive) with a renal biopsy diagnosis of primary glomerulonephritis have been compared. Total foetal loss was similar for both groups (18% Vs 16%) as was perinatal mortality (6% Vs 7%). Prematurity rates of hypertensive and normotensive groups were also similar (24% Vs 15%) but 25% of infants of mothers in the hypertensive group were small for gestational age compared with only 4% in the normotensive group (p