Jacob Sevastos

Goodpasture's disease: Antiglomerular basement membrane disease

Goodpasture’s disease, also known as antiglomerular basement membrane disease (anti-GBM), is a rare but important cause of pulmonary haemorrhage (PH) and rapidly progressive crescentic glomerulonephritis (GN) that leads to irreversible renal failure. As an autoimmune disease, it is characterized by the production of pathogenic autoantibodies to the NC1 domain of the alpha 3 chain of type IV collagen (the Goodpasture antigen), 1

Acute kidney injury due to crystalluria following acute valacyclovir overdose

A 49-year-old man was admitted to the hospital with an acute overdose of olanzapine 2.5 g, venlafaxine-XR 4.2 g, valacyclovir 30 g, and alcohol (blood alcohol concentration on admission 0.21%). On arrival he was hypotensive (87/57 mm Hg), tachycardic (135/min), and sedated with a lactic acidosis (5.8 mmol/l). His blood pressure increased to 129/75 mm Hg following 2 l fluid resuscitation and venous lactate concentration decreased to 2.1 mmol/l. His serum creatinine concentration was 104 μmol/l on admission (baseline concentration 65 μmol/l), but increased to 223 μmol/l the following day in the absence of other clinical abnormalities. Acyclovir-induced crystalluria was suspected, and so oral fluid intake was increased to 4–5 l/day. The creatinine concentration peaked at 538 μmol/l at 72 h and resolved over 1 week. Analysis of urine from the time of admission demonstrated pH 5.0, specific gravity 1.015, and birefringent needle-shaped crystals (see Figure 1) on a spun specimen (matching previous descriptions of acyclovir crystals). Repeat urinalysis during recovery was normal. Thrombocytopenia was also noted, with a nadir of 87 × 109/l at 48 h post-ingestion.

Clinical Pharmacokinetics in Kidney Disease Fundamental Principles

Kidney disease is an increasingly common comorbidity that alters the pharmacokinetics of many drugs. Prescribing to patients with kidney disease requires knowledge about the drug, the extent of the patients altered physiology, and pharmacokinetic principles that influence the design of dosing regimens. There are multiple physiologic effects of impaired kidney function, and the extent to which they occur in an individual at any given time can be difficult to define. Although some guidelines are available for dosing in kidney disease, they may be on the basis of limited data or not widely applicable, and therefore, an understanding of pharmacokinetic principles and how to apply them is important to the practicing clinician. Whether kidney disease is acute or chronic, drug clearance decreases, and the volume of distribution may remain the same or increase. Although in CKD, these changes progress relatively slowly, they are dynamic in AKI, and recovery is possible depending on the etiology and treatments. This, and the use of kidney replacement therapies further complicate attempts to quantify drug clearance at the time of prescribing and dosing in AKI. The required change in the dosing regimen can be estimated or even quantitated in certain instances through the application of pharmacokinetic principles to guide rational drug dosing. This offers an opportunity to provide personalized medical care and minimizes adverse drug events from either under- or overdosing. We discuss the principles of pharmacokinetics that are fundamental for the design of an appropriate dosing regimen in this review.

A 25 year Review of Combined Cardiac and Renal Transplant Outcomes in Patients with End Stage Cardiac Failure on Renal Replacement Therapy. A Single Center Experience.

Background: Combined heart and kidney transplantation has been shown to be a viable option for patients who have concurrent end stage cardiac and renal failure. However there is limited long term survival data that compares the outcomes of patients undergoing combined heart-kidney transplantation to patients undergoing solitary cardiac transplantation. There is also limited data on patients with end stage cardiac failure who are on concurrent renal replacement therapy prior to organ transplantation and their outcomes. This study reviews the short and long term outcomes of combined heart kidney transplantation over a 25 year period in comparison to solitary cardiac transplantation in a majority of patients undergoing renal replacement therapy at time of transplant listing. Methods and Results: In total there were 16 patients who underwent combined heart and kidney transplantation in the period between October 1990 and June 2014 (including heart and kidney re-transplantation) with 14 patients (87.5%) on renal replacement therapy at time of combined procedure. They were listed for combined heart and kidney transplantation as they fulfilled our institution’s criteria for irreversible end-stage heart and kidney failure. Retrospective review of patient data from the transplant database, patient case notes and post-mortem reports were carried out. Statistical analysis was then performed on key patient demographics alongside actuarial survival analysis, which were then graphically annotated. IRB approval was obtained and informed consent from patients was also obtained. The mean (SD) recipient age was 42 (13) years and there were 3 females. Dilated cardiomyopathy was the most common primary cardiac pathology (50%) whilst ischemic nephrosclerosis (25%) and glomerulonephritis (25%) were the most common primary renal pathologies. Most patients experienced NYHA class IV symptoms (62.5%). The average wait time to transplantation at our institution was 12 months. There was no operative mortality. The cumulative 1 year survival in the combined transplant group was 0.75 with 4 out of 16 mortalities within the first year (25%). In comparison the cumulative 1 year survival of the heart only transplant group was 0.86 with 116 mortalities within the first year over a 25 year period. Cumulative survival at 5, 10, 15 and 25 years for the combined transplant group was 0.69, 0.55, 0.437 and 0.437 respectively. In comparison cumulative survival of the heart only transplant group at the 5, 10, 15 and 25 year mark was 0.76, 0.59, 0.45 and 0.23 respectively. The incidence of cardiac rejection episodes in the study time was 9 out of 16 (56%) versus 3/16 (19%) who had renal rejection. In the study period there was 1 death out of 7 deaths due to dual graft failure. Conclusions: Combined sequential cardiac and renal transplantation has good shortand long-term outcomes for patients with coexisting end stage cardiac and renal failure. At the ten year mark actuarial survival for combined heart and kidney transplantation is equivalent to cardiac transplantation alone. Received Date: February 08, 2016; Accepted Date: July 12, 2016; Published Date: July 15, 2016 Citation: Anthony, C., et al. A 25 Year Review of Combined Cardiac and Renal Transplant Outcomes in Patients with End Stage Cardiac Failure on Renal Replacement Therapy. A Single Center Experience. (2016) J Heart Cardiol 2(2): 59-67.

Outcomes of simultaneous heart-kidney and lung-kidney transplantations: The Australian and New Zealand experience

Heart or lung transplantation alone in individuals with significant pre‐existing renal impairment results in high mortality and morbidity. Simultaneous heart–kidney (SHK) or simultaneous lung–kidney (SLK) transplantation may be considered in patients with dual organ failure not suitable for single organ transplantation.

Fibromuscular hyperplasia as a cause of transplant renal artery stenosis

SUMMARY:  There are several causes of transplant renal artery stenosis, resulting in hyperten‐ sion and renal dysfunction. Rarely, fibromuscular hyperplasia may cause such a presentation, and this case report discusses the historical, diagnostic and management issues pertaining to this rare situation.

Life-Saving Combined Heart–Kidney Transplantation in a Previous Sequential Heart and Kidney Transplant Recipient

Purpose Solid organ re-transplantation in the context of allograft failure is a challenging clinical and ethical problem. Ideally, solid organ re-transplantation after initial allograft failure should be performed in all recipients, but this is often not clinically or logistically feasible. Methods This report details what we believe is the first combined heart–kidney transplant in a recipient of a previous sequential heart and kidney transplant. Results Eight years after a combined heart and kidney transplant after initially receiving a sequential heart and kidney transplant, a 31-year-old man is doing extremely well, with no rejection episodes or significant complications after transplantation. Summary This case confirms that combined heart and kidney transplantation is a viable option for tackling the complex issue of graft failure in recipients of previous cardiac and renal grafts. LEARNING POINTS Good short- and long-term outcomes following combined heart–kidney transplantation can be achieved in patients with multi-system end-organ dysfunction. Advances in immunosuppressant therapy have enabled multiple transplantation procedures from different donors in a single recipient. We describe the first recipient in the world of combined heart–kidney transplantation on a background of previous sequential heart–kidney transplantation.

Clinical Pharmacokinetics in Kidney Disease: Application to Rational Design of Dosing Regimens

A change in pharmacokinetics can alter drug exposure and predispose the patient to either over- or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between individuals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drugs properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.

Tenckhoff Catheter Implantation In Refractory Ascites Due To Right Heart Failure

Tenckhoff catheter implantation and modified peritoneal dialysis as a novel therapeutic approach in diuretic resistant congestive heart failure: a single-centre case-series. Background: Progressive renal insufficiency and diuretic resistance represent significant challenges in the management of advanced heart failure, particularly in the context of intractable ascites due to Right Heart Failure (RHF). There is growing interest in the potential use of intermittent paracentesis and peritoneal dialytic ultra-filtration in this setting but clinical experience is limited. Methods: We undertook retrospective analysis of changes in the following clinical parameters in six patients (66% males, average age 53 years) who underwent Tenckhoff catheter implantation (TCI) for the management of RHF-related intractable ascites i) body weight; ii) number of heart failure related admissions and time spent in hospital; and iii) diuretic requirements. Student t-test was performed to analyse statistical significance. Results: Follow-up ranged from 4 to 16 weeks post TCI. Compared to immediately prior to TCI: i) 83% (5/6) of patients experienced an improvement in renal function; ii) average weight fell from 72.2 + 4.7 to 67.7 + 3.9 kg (mean + SEM, p = 0.054); iii) none of the patients have required heart failure related admission compared to an average number of 40 days in hospital over 6.7 admissions in the twelve months preceding TCI and iv) frusemide dose decreased from 263 + 49 to 140 + 50 mg/day, p = 0.051). All patients report a subjective improvement in overall wellbeing and quality of life. One patient developed peritonitis which was controlled with antibiotic treatment without needing catheter removal. Conclusion: Our experience supports the use of TCI as a therapeutic modality in patients with RHF and intractable ascites resistant to medical management. Received Date: February 08, 2016 Accepted Date: March 22, 2016 Published Date: March 29, 2016 Citation: Anthony, C., et al. Tenckhoff Catheter Implantation in Refractory Ascites Due to Right Heart Failure. (2016) J Heart Cardiol 2(2): 1-5. DOI: 10.15436/2378-6914.16.020

Dose-Adjusted Beta-Lactam Antibiotic-Induced Encephalopathy in a Patient with End-Stage Renal Impairment: A Case Report

Introduction: Despite adherence to current guidelines regarding dose adjustment and drug-level monitoring, beta-lactam-induced encephalopathy can still occur in the setting of chronic renal impairment. Case Report: We report what we believe is the first case of piperacillin- and tazobactam-induced encephalopathy in a patient with pre-existing cefepime-induced encephalopathy in the context of end-stage kidney disease despite adequate dose adjustment for renal impairment.