Hepatitis C and Kidney Transplantation

Hepatitis C virus (HCV) infection is relatively common among patients with end-stage kidney disease (ESKD) on dialysis and kidney transplant recipients. HCV infection in hemodialysis patients is associated with an increased mortality due to liver cirrhosis and hepatocellular carcinoma. The severity of hepatitis C-related liver disease in kidney transplant candidates may predict patient and graft survival after transplant. Liver biopsy remains the gold standard in the assessment of liver fibrosis in this setting. Kidney transplantation, not haemodialysis, seems to be the best treatment for HCV+ve patients with ESKD. Transplantation of kidneys from HCV+ve donors restricted to HCV+ve recipients is safe and associated with a reduction in the waiting time. Simultaneous kidney/liver transplantation (SKL) should be considered for kidney transplant candidates with HCV-related decompensated cirrhosis. Treatment of HCV is more complex in hemodialysis patients, whereas treatment of HCV recurrence in SLK recipients appears effective and safe

Recent Advances in the Pathogenesis and Management of Cast Nephropathy (Myeloma Kidney)

Multiple myeloma is an incurable plasma cell malignancy that is often accompanied by renal failure; there are a number of potential causes of this, of which cast nephropathy is the most important. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. Consequently, there is an ongoing focus on the pathological basis of cast nephropathy and the optimal treatment regimens in this setting, including effective chemotherapy regimens to reduce light chain production and emerging extracorporeal techniques to remove circulating light chains. This paper bridges recent advances in the pathogenesis and management of cast nephropathy in multiple myeloma

Optimal management of acute kidney injury in critically ill patients with invasive fungal infections being treated with liposomal amphotericin B.

Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully used in the setting of AKI. The first was Aspergillus infection in a 63-year-old man with bleeding oesophageal varices related to advanced liver disease. The second was gastrointestinal mucormycosis in a 74-year-old man who developed a small bowel obstruction following an autologous stem cell transplant for mantle cell lymphoma. The third was a Fusarium infection in a 32-year-old woman on immunosuppression for a bilateral lung transplant for cystic fibrosis. In all three cases, liposomal amphotericin B was required for urgent management of the patient's IFI. We discuss the rationale for treatment with a potentially nephrotoxic agent in this setting

Association between Periodontitis and mortality in stages 3-5 Chronic Kidney Disease: NHANES III and linked mortality study

INTRODUCTION: Periodontitis may add to the systemic inflammatory burden in individuals with chronic kidney disease (CKD), thereby contributing to an increased mortality rate. This study aimed to determine the association between periodontitis and mortality rate (all‐cause and cardiovascular disease‐related) in individuals with stage 3–5 CKD, hitherto referred to as “CKD”. METHODS: Survival analysis was carried out using the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality data. Cox proportional hazards regression was employed to assess the association between periodontitis and mortality, in individuals with CKD. This association was compared with the association between mortality and traditional risk factors in CKD mortality (diabetes, hypertension and smoking). RESULTS: Of the 13,784 participants eligible for analysis in NHANES III, 861 (6%) had CKD. The median follow‐up for this cohort was 14.3 years. Adjusting for confounders, the 10‐year all‐cause mortality rate for individuals with CKD increased from 32% (95% CI: 29–35%) to 41% (36–47%) with the addition of periodontitis. For diabetes, the 10‐year all‐cause mortality rate increased to 43% (38–49%). CONCLUSION: There is a strong, association between periodontitis and increased mortality in individuals with CKD. Sources of chronic systemic inflammation (including periodontitis) may be important contributors to mortality in patients with CKD

Fractures in kidney transplant recipients : a comparative study between England and New York State

Objectives: Fractures are associated with high morbidity and are a major concern to kidney transplant recipients. There has not been any comparative analysis conducted between countries in the contemporary era to inform future international prevention trials. Materials and Methods: Data were obtained from the Hospital Episode Statistics and the Statewide Planning and Research Cooperative databases on all adult kidney transplants performed in England and New York State respectively (2003-2013) and on post-transplant fracture-related hospitalization (2003-2014). Results: In total, 18,493 English and 11,602 New York State kidney transplant recipients were included. Overall, 637 (3.4%) English and 398 (3.4%) New York State recipients sustained a fracture giving an unadjusted event rate of 7.0 and 5.9 per 1000 years respectively (P=0.948). A total of 147 (0.8%) English and 101 (0.9%) New York State recipients sustained a hip fracture, giving an unadjusted event rate of 1.6 and 1.5 per 1000 years respectively (P=0.480). There were no differences in the cumulative incidence of all fractures or hip fractures. One-year mortality after any fracture (9% and 11%) or after a hip fracture (15% and 17%) was not different between cohorts. Conclusions: Contemporaneous English and New York State kidney transplant recipients have very similar fracture rates and mortality post-fracture

Expression of calponin in periglomerular myofibroblasts of rat kidney with experimental chronic injuries

Our previous research demonstrated that calponin-immunoreactivity was localized in myofibroblasts of the periglomerular region of human kidney specimens obtained at the time of transplantation from organ recipients. In the present study we examined calponin expression in two chronic nephropathy models, puromycin aminonucleoside (PAN) nephropathy and subtotal nephrectomy (SNx), to investigate the role of calponin in chronic renal injury. Male Sprague-Dawley rats were used, and both nephropathy models were established at 1, 2, 4, and 8 weeks after surgery. There were no periglomerular calponin-positive cells in sham, PAN 1 and 2 week, and SNx 1, 2, and 4 week groups. In SNx 8 week and PAN 4 and 8 week groups, only a few glomeruli with periglomerular calponin-reactivity, which covered half or a very small part of the periglomerular space, were observed. All glomeruli with periglomerular calponin-reactivity showed sclerotic changes, especially thickening of parietal epithelial cells (PECs). In conjunction with our previous report, this data represents the first documentation of the expression of calponin in renal myofibroblasts. We suggest that interactions between PECs and calponin-positive myofibroblasts may play a key role in the late stage of glomerulosclerosis

Calciphylaxis following kidney transplantation: a case report

Introduction: Calciphylaxis occurring after kidney transplantation is rare and rarely reported. It results in chronic non-healing wounds and is associated with a poor prognosis and is often fatal. We present a case of proximal lower limb calciphylaxis that occurred early after kidney transplantation. The patient had no classic associated risk factors. He had previously had a total parathyroidectomy but had normal serum calcium-phosphate product and parathyroid hormone levels. The clinical outcome of this case was favorable and highlights some fundamental issues relating to management. Case prsentation: A 70-year-old British Caucasian man with end-stage renal failure secondary to IgA nephropathy presented six months post kidney transplantation with cutaneous calciphylaxis lesions involving the medial aspect of the thigh bilaterally. Conclusion: To the best of our knowledge, this is the first reported case of rapid onset cutaneous calciphylaxis occurring soon after kidney transplantation that was associated with a favorable outcome. Cutaneous calciphylaxis lesions should be promptly managed with meticulous wound care, antimicrobial therapy and the correction of calcium-phosphate product where indicated

European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): A randomised control trial

<p>Abstract</p> <p>Background</p> <p>Renal failure is a frequent complication of multiple myeloma and when severe is associated with a greatly increased morbidity and mortality. The principal cause of severe renal failure is cast nephropathy, a direct consequence of high concentrations of monoclonal free light chains (FLCs) in patients' sera. FLC removal by extended haemodialysis, using a high cut-off dialyser, has recently been described as a novel therapeutic option.</p> <p>Methods</p> <p>The <b>EU</b>ropean trial of free <b>LI</b>ght chain removal by ex<b>TE</b>nded haemodialysis in cast nephropathy (EuLITE) trial is a prospective, randomised, multicentre, open label clinical trial to investigate the clinical benefits of FLC removal haemodialysis in patients with cast nephropathy, dialysis dependent acute renal failure and <it>de novo </it>multiple myeloma. Recruitment commenced in May 2008. In total, 90 patients will be recruited. Participants will be randomised, centrally, upon enrolment, to either trial chemotherapy and FLC removal haemodialysis or trial chemotherapy and standard high flux haemodialysis. Trial chemotherapy consists of bortezomib, doxorubicin and dexamethasone. FLC removal haemodialysis is undertaken with two Gambro HCO 1100 dialysers in series using an intensive treatment schedule. The primary outcome for the study is independence of dialysis at 3 months. Secondary outcomes are: duration of dialysis, reduction in serum FLC concentrations; myeloma response and survival.</p> <p>Hypothesis</p> <p>FLC removal haemodialysis will increase the rate of renal recovery in patients with severe renal failure secondary to cast nephropathy in <it>de novo </it>multiple myeloma.</p> <p>Trial registration</p> <p>ISRCTN45967602</p