Life on the list: an exploratory study of the life world of individuals waiting for a kidney transplant

Kidney transplantation is the treatment of choice for many individuals with end stage renal disease (ESRD), as transplantation is reported to offer a greater quality of life than renal dialysis. At the end of March 2008 there were 6980 people on the active transplant list for kidney or kidney and pancreas transplants. However, during the previous year a total of 1453 deceased donor kidney transplants were carried out1, illustrating the mismatch between demand for and availability of kidneys for transplant. Whilst the Government has pledged to improve transplant services and to address the organ shortage, individuals on the kidney transplant list are currently facing an average wait of more than two years. Individuals waiting for a kidney transplant face complex challenges, which are currently poorly researched. An insight into the experience of waiting for a kidney transplant and how individuals interpret that wait could contribute to clinical knowledge and lead to improved support for these individuals. It could also raise public awareness about the issues involved in waiting for a kidney transplant, potentially encouraging donatio

Dual mTOR/PI3K inhibition limits PI3K-dependent pathways activated upon mTOR inhibition in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of kidney cysts leading to kidney failure in adulthood. Inhibition of mammalian target of rapamycin (mTOR) slows polycystic kidney disease (PKD) progression in animal models, but randomized controlled trials failed to prove efficacy of mTOR inhibitor treatment. Here, we demonstrate that treatment with mTOR inhibitors result in the removal of negative feedback loops and up-regulates pro-proliferative phosphatidylinositol 3-kinase (PI3K)-Akt and PI3K-extracellular signal-regulated kinase (ERK) signaling in rat and mouse PKD models. Dual mTOR/PI3K inhibition with NVP-BEZ235 abrogated these pro-proliferative signals and normalized kidney morphology and function by blocking proliferation and fibrosis. Our findings suggest that multi-target PI3K/mTOR inhibition may represent a potential treatment for ADPKD

Troponins, Acute Coronary Syndrome and Renal Disease: From Acute Kidney Injury Through End-stage Kidney Disease

The diagnosis of acute coronary syndromes (ACS) is heavily dependent on cardiac biomarker assays, particularly cardiac troponins. ACS, particularly non-ST segment elevation MI, are more common in patients with acute kidney injury, chronic kidney disease (CKD) and end-stage kidney disease (ESKD), are associated with worse outcomes than in patients without kidney disease and are often difficult to diagnose and treat. Hence, early accurate diagnosis of ACS in kidney disease patients is important using easily available tools, such as cardiac troponins. However, the diagnostic reliability of cardiac troponins has been suboptimal in patients with kidney disease due to possible decreased clearance of troponin with acute and chronic kidney impairment and low levels of troponin secretion due to concomitant cardiac muscle injury related to left ventricular hypertrophy, inflammation and fibrosis. This article reviews the metabolism and utility of cardiac biomarkers in patients with acute and chronic kidney diseases. Cardiac troponins are small peptides that accumulate in both acute and chronic kidney diseases due to impaired excretion. Hence, troponin concentrations rise and fall with acute kidney injury and its recovery, limiting their use in the diagnosis of ACS. Troponin concentrations are chronically elevated in CKD and ESKD, are associated with poor prognosis and decrease the sensitivity and specificity for diagnosis of ACS. Yet, the evidence indicates that the use of high-sensitivity troponins can confirm or exclude a diagnosis of ACS in the emergency room in a significant proportion of kidney disease patients; those patients in whom the results are equivocal may need longer in-hospital assessment

Climate change and the kidney

The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role not only in protecting the host from heat and dehydration but also is an important site of heat-associated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.Published versio

A Primer on Kidney Transplantation: Anatomy of the Shortage

Kidneys are unique among the solid organs due to the combination of the low risk of living donation, the feasibility of sustaining life on dialysis for several years following kidney failure, and Medicare coverage of dialysis and transplantation for kidney patients. Despite these advantages, thousands of Americans die each year while waiting for a kidney transplant, and the waiting list grows each year. In this kidney transplantation primer, we provide a quantitative description of the kidney shortage and discuss future trends and possible solutions. We demonstrate that the current system provides only about half as many kidneys as are needed for transplantation and the gap cannot be eliminated through an increase in deceased donation alone, because most kidneys from suitable deceased donors are already procured. The prospects for increasing living donations under the current system are also dim. Donations from living kidney donors have declined from their 2003 peak and nearly all living kidney donations are directed by the donor, usually to family members, rendering the current account of living kidney donation as “altruistic” somewhat misleading. For all of these reasons, we believe the time is ripe to reconsider financial incentives for kidney donation. Needless to say, a system that provided financial rewards for living donors could produce unsavory consequences, and would have to be carefully designed and managed. But without such a system, the most likely version of the future is a continuation of unnecessarily high rates of death and disability from kidney failure

Emerging key roles for P2X receptors in the kidney

P2X ionotropic non-selective cation channels are expressed throughout the kidney and are activated in a paracrine or autocrine manner following the binding of extracellular ATP and related extracellular nucleotides. Whilst there is a wealth of literature describing a regulatory role of P2 receptors (P2R) in the kidney, there are significantly less data on the regulatory role of P2X receptors (P2XR) compared with that described for metabotropic P2Y. Much of the historical literature describing a role for P2XR in the kidney has focused heavily on the role of P2X1R in the autoregulation of renal blood flow. More recently, however, there has been a plethora of manuscripts providing compelling evidence for additional roles for P2XR in both kidney health and disease. This review summarizes the current evidence for the involvement of P2XR in the regulation of renal tubular and vascular function, and highlights the novel data describing their putative roles in regulating physiological and pathophysiological processes in the kidney

Kidney transplantation. Modern trends in kidney transplantation.

Trends in renal transplantation stem from recognition of the virtues and drawbacks of this kind of treatment and from a better appreciation of the interrelationship between transplantation and dialysis

A new outlook towards kidney injuries

Acute and chronic progression of injury to the kidney leads to the failure of the renal system and has become an increasingly important cause of morbidity and mortality. Present diagnosis detects the condition only after irreversible loss of 70 percent of kidney function. Current research is focused only on the clinical manifestations after the kidney injuries and not towards the exact cause of the condition. Here we propose a new outlook- that there is an involvement of a pathogen in the pathogenesis of kidney injuries. Basis for our proposal is given by the similarity of the pathogenesis events occurring between a classical example of hepatitis and kidney injuries. Furthermore, literature regarding the role of early kidney injury biomarkers in innate immunity indicates the involvement of the pathogen. Research in this theme possesses a strong possibility in the development of therapeutic, preventive and management strategies for the acute and chronic kidney injuries

Diabetic microangiopathy in Type 1 (insulin-dependent) diabetic patients after successful pancreatic and kidney or solitary kidney transplantation

To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulin-dependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n=17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow / velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46±2 mm Hg to 63±3 mmHg), reoxygenation time (fall from 224±12s to 114±6s) and laser speckle measurement (rise from 4.2±1.7 to 5.6±1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation

Diabetes and kidney cancer: A direct or indirect association?

A positive association between diabetes and kidney cancer has been reported in several investigations, but it is unclear whether diabetes or its complications account for this association. Recent advances in estimating direct associations may be useful for elucidating the association between diabetes and kidney cancer. Therefore, we performed a case-control analysis to evaluate whether the direct association between diabetes and kidney cancer is the primary concern in this exposure-outcome relation. Discharge data (with International Classification of Diseases – 9 codes) from 2001 for hospitals throughout Florida were used to construct a case-control population of inpatients aged ≥45 years. Cases (n=1,909) were inpatients with malignant kidney cancer and controls (n=6,451) were inpatients with motor vehicle injuries. Diabetes status was ascertained for cases and controls. Covariates that required adjustment to estimate the total (age, gender, ethnicity, obesity, and smoking) and direct (age, gender, ethnicity, obesity, smoking, hypertension, and kidney disease) associations were identified in a directed acyclic graph. Binary logistic regression was used to estimate the adjusted total and direct odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of kidney cancer for diabetics. The odds of kidney cancer were higher for inpatients with diabetes than inpatients without diabetes when estimating the total association (OR=1.27, 95%CI: 1.10, 1.47) but attenuated when estimating the direct association (OR=1.08, 95%CI: 0.93, 1.25). Our findings provide preliminary insight that the direct association between diabetes and kidney cancer may not be the primary concern in this exposure-outcome relation; indirect pathways (i.e. diabetic complications) may have greater influence on this relation. A similar analysis using longitudinal data with appropriately measured covariates may provide more definitive conclusions and could have implications for kidney cancer prevention among diabetics