End Stage Renal Failure

Childhood chronic kidney disease commonly progresses toward end-stage renal failure, largely independent of the underlying disorder, once a critical impairment of renal function has occurred. Hypertension and proteinuria are the most important independent risk factors for renal disease progression. Therefore, current therapeutic strategies to prevent progression aim at controlling blood pressure and reducing urinary protein excretion. Renin-angiotensin-system (RAS) antagonists preserve kidney function not only by lowering blood pressure but also by their antiproteinuric, antifibrotic, and anti-inflammatory properties. Intensified blood pressure control, probably aiming for a target blood pressure below the 75th percentile, may exert additional renoprotective effects. Other factors contributing in a multifactorial manner to renal disease progression include dyslipidemia, anemia, and disorders of mineral metabolism. Measures to preserve renal function should therefore also comprise the maintenance of hemoglobin, serum lipid, and calcium-phosphorus ion product levels in the normal range.

Objective. The ItalKid Project is a prospective, population-based registry that was started in 1990 with the aim of assessing the epidemiology of childhood chronic renal failure (CRF), describing the natural history of the disease, and identifying factors that influence its course. This article reports the epidemiologic results.

Objective. The ItalKid Project is a prospective, population-based registry that was started in 1990 with the aim of assessing the epidemiology of childhood chronic renal failure (CRF), describing the natural history of the disease, and identifying factors that influence its course. This article reports the epidemiologic results.

ObjectiveDiabetic nephropathy is a debilitating disease that leads to end-stage renal failure in the Western world. Hyperglycemia is the initiating factor in several chronic diabetic complications which mediates increased oxidative stress and eventually the increased production of vasoactive factors and extracellular matrix proteins. We hypothesized that curcumin, a potent antioxidant, might be beneficial in preventing the development of diabetic nephropathy

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population.

Chronic kidney disease (CKD), a major worldwide public-health problem which affects about 10% of the population, has an increased annual incidence rate of about 5-8%. This increased incidence is mainly due to type 2 diabetes and hypertension and the increasing incidence of elderly patients with CKD. Although the progression to end-stage renal failure (ESRF) is mainly based upon the underlying disease, comorbid conditions such as an initial low renal function, severe proteinuria, and high levels of blood pressure also play important roles in the development of ESRF. Since experimental and clinical evidence suggest that angiotensin II plays a central role in the progression of CKD, pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists has been suggested as firstline treatment for hypertension and prevention of ESRF in these patients. Aliskiren, a novel renin inhibitor is also a promising medical intervention. However, independently of the category of the drugs used, low target blood pressure levels seem to be equally or more important for the delay or prevention of CKD. In this review the results of studies with pharmacological inhibition of the RAAS in patients with diabetic and nondiabetic nephropathy is discussed.

Diabetic nephropathy is now the most common cause of end-stage renal failure in many countries of the world. Despite increasing implementation of preventive treatment, the chance that an individual diabetic patient will reach end-stage renal failure has been increasing rather than decreasing during recent decades. Current dietary habits in The Netherlands and the rest of the Western world are slowly shifting from relatively alkalinizing (e.g., potatoes and vegetables) toward more acidifying (e.g., rice and meat). Moreover, immigrants who consumed traditional diets in their homelands, usually adapt to Western dietary habits. This phenomenon of diet acculturation could, for instance, be involved in the up to 40 times higher chance of development of end-stage renal failure in association with diabetes in South-Asian immigrants compared with whites, in Western countries. High ingestion of nonvolatile acids with food increases susceptibility for progression to end-stage renal failure. These high dietary acid loads lead to compensatory increases in renal acid excretion and ammoniagenesis. The price paid for maintenance of acid-base homeostasis is renal tubulointerstitial injury, with subsequent decline in renal function and induction of hypertension. The tendency for metabolic acidosis that results from the changing dietary habits could be corrected by a shift toward more alkalinizing food. We hypothesize that promoting such a shift can prevent the epidemic of end-stage renal failure in diabetes.

In this paper, I present an analysis of the unique and storied history of End Stage Renal Disease treatment in the United States. Framed through the recounting of my own father’s experiences with the disease and his eventual kidney transplant, I attempt to construct a narrative that accurately portrays the unique aspects of living with ESRD, particularly the sense of “persistent liminality” that it engenders, and how these aspects have come to shape the course of political, scientific, medical, and social approaches to ESRD and its treatment. I aim to portray the unique “ESRD experience” in order to properly contextualize information about current practices with regard to its treatment, including Medicare policies, dialysis, and kidney transplantation.
This paper also aims to evaluate the role that personal appeals for organ donations have played throughout the history of treatment for ESRD and of organ transplantation, with particular attention to the diverse relationships that such appeals have had with public policy regarding organ transplantation—at times seeming to animate policy developments, while at other times assuming an antagonistic role vis-à-vis the medical and legal establishments—and the further ethical issues implicated by the advent of social media as a tool to facilitate these exchanges. In Part I, I will recount the history of modern treatment for kidney disease, and how its development set up a paradigm that deeply entwined the federal government and the medical establishment. I will discuss the complex history of the earliest widely-used treatment for kidney failure—dialysis—paying special attention to the issues of scarcity and allocation that have complicated this treatment since the opening of the first long-term dialysis clinics in the early 1960s. I will discuss how the success of kidney transplantation created new problems of supply and demand that resemble those associated with dialysis in the past. I will recount the history of legislation related to kidney disease and organ donation, including a discussion of the role that personal emotional appeals have played in shaping public policy related to the treatment of kidney disease, even before transplantation became the preferred method of treatment. In Part II, I will provide statistics to illustrate the gravity of the issues that characterize our current system of regulating organ transplantation. Then, I will describe the values that motivate our organ donation and allocation system, and the conflicts they can engender. In Part III, I aim to further elucidate the profound moral issues implicated in organ transplantation by discussing the experience of having end stage renal disease, and relating the reality of this experience to an analysis of the rhetoric surrounding kidney transplantation in the United States. Part IV will address various issues concerning directed donations from living organ donors. First, I will discuss the notable absence of regulation with regard to organ donations from living donors, explaining why this regulatory gap exists, and how it has led to further controversy and dysfunction within the organ transplantation system. Second, I will discuss concerns unique to living kidney donation, and how the medical and legal establishments have responded to these concerns in crafting the transplant process as it operates today. Next, I will analyze trends in living donation, specifically the increasing popularity of non-related directed donations. I will discuss the ethical issues implicated in this trend, including the permissibility of directed donation, how certain types of directed donation conflict with the values that constitute the backbone of our current organ transplantation system, and the question of risk to both donor and recipient. I will then specifically address the role of social media and the Internet in facilitating this trend, and the ways in which new social media platforms to facilitate living donation may serve to exacerbate inequalities in organ allocation. In Part V, I will propose a way to harness the power of social media in order to facilitate increased donation, and make several suggestions for improving our policy regarding living organ donation.

Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease. Methods: We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry. Results: The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients' gender. Conclusions: The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/ decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.

Blood glucose monitoring is important in optimizing long-term outcomes in diabetic patients. Reliance on near-patient testing and the use of longer term measures of glycation are the current cornerstones. However, as this review details, there are significant problems using blood tests as measures of metabolic control in uremic diabetic patients. Am J Kidney Dis 41:523-531.

The outcome of pregnancy in patients with end-stage renal failure has long been considered to be extremely poor, and the literature concerning pregnancy while on dialysis is rather scarce. We reviewed the records of five pregnancies in dialysis patients and performed a national survey on this topic. The dialysis technique and dialysis dose, the effects of erythropoietin (EPO), and the evolution of blood pressure levels in our patients are presented. The dose of EPO had to be increased to maintain the hemoglobin level at 10 to 11 g/dL. There was no case of EPO-related hypertension and no need for transfusion. The obstetric data of the national survey, including our own patients, were analyzed. The incidence of pregnancy going beyond the first trimester was 0.3 per 100 patient-years (15 cases in 1,472 females of childbearing age treated, for a total of 4,545 patient-years). In all but one patient initiating pregnancy while already on dialysis, the frequency and dose of dialysis were increased (to a weekly Kt/V of six to eight in our personal cases). The outcome was successful in 50% of pregnancies occurring in hemodialyzed patients and in 80% of patients who started dialysis after initiation of pregnancy. Polyhydramnios was found in eight of 13 cases and growth retardation in two of nine cases. The incidence of low birth weight and prematurity was 100%, and cesarean section was performed in 66% of successful pregnancies. In successful pregnancies, we found a correlation between birth weight and dose of dialysis. Our findings confirm the remarkable improvement in the prognosis of pregnancy in dialysis patients in recent years.

Renal function in utero deals chiefly with urine production rather than the excretion of metabolites, which are cleared by the placenta. Fetal renal impairment (FRI) in bilateral renal disease thus presents as oligohydramnios or anhydramnios; this can lead to lung hypoplasia and early neonatal death. As in the adult, FRI can be divided into prerenal, renal and postrenal causes. Causes of prerenal FRI include intrauterine growth restriction, unbalanced intertwin transfusion in monochorionic twins and maternal drug ingestion. Bilateral renal agenesis, multicystic dysplasia and both the autosomal dominant and recessive forms of polycystic kidney disease are examples of renal causes, whereas postrenal etiologies are usually caused by lower urinary tract obstruction (LUTO). When both kidneys are affected and there is severe mid-trimester oligohydramnios, the prognosis is poor. Although animal studies have shown that prolonged LUTO leads to lung hypoplasia and renal damage, and that decompression of the fetal kidney in early pregnancy restores fetal pulmonary and renal function, the value of fetal therapy such as vesico-amniotic shunting remains controversial, with a high procedure-related complication rate and a high incidence of end-stage renal failure in childhood. Fetal cystoscopic treatment of posterior urethral valves in utero may obviate some of these difficulties but remains an investigational procedure.

Long-term prognosis of patients with type-1 diabetes mellitus and end-stage renal failure appears to be better after kidney transplantation compared with dialysis. Controversy exists about the additional benefit of a simultaneously transplanted pancreatic graft. We studied the effect on mortality of simultaneous pancreas-kidney transplantation compared with kidney transplantation alone from regional differences in transplantation protocols.All 415 patients with type-1 diabetes (aged 18–52 years) who started renal-replacement therapy in the Netherlands between 1985 and 1996 were included in the analysis. Patients were allocated to a centre based on their place of residence at onset of renal failure. In the Leiden area, the primary intention to treat was with a simultaneous pancreas-kidney transplantation, whereas in the non-Leiden area, kidney transplantation alone was the predominant type of treatment. All patients were followed up to July, 1997. Analyses, mortality, and graft failure were by Cox proportionalhazard model adjusted for age and sex.Simultaneous pancreas-kidney transplantation was done in 41 (73%) of 56 transplanted patients in the Leiden area compared with 59 (37%) of 158 transplanted patients in the non-Leiden area (p<0·001). The hazard ratio for mortality after the start of renal-replacement therapy was 0·53 (95% CI, 0·36–0·77, p<0·001) in the Leiden area compared with the non-Leiden area. When just the transplanted patients were analysed the mortality ratio was 0·4 (95% CI 0·20–0·77, p=0·008) and was independent of duration of dialysis and early transplant-related deaths. Equal survival was found for patients on dialysis only.These data support the hypothesis that simultaneous pancreas-kidney transplantation prolongs survival in patients with diabetes and end-stage renal failure.

Kidney transplantation (Tx) has evolved as the treatment of choice in patients with end-stage renal failure. Unfortunately, after Tx, there is a gradual deterioration in graft function and the patient develops chronic allograft nephropathy (CAN). This can happen as soon as 3 months or as late as many years. Therefore, CAN is the major clinical problem in renal Tx, as the pathophysiological mechanisms remain obscure. In this article, we try to review the risk factors and causes of CAN and their possible explanation. In conclusion, and as a consequence from the bibliography, we can see clearly that CAN is the result of interplay or synergistic action between alloantigen-dependent and alloantigenindependent factors, which each act with different significance at each stage in the life span of a transplant. The exactly pathogenesis of CAN is elusive but we have a common trigger (tissue injury) and common response (inflammatory response).

The rising prevalence of chronic kidney disease (CKD) and subsequent end stage renal failure necessitating renal replacement therapy has profound consequences for affected individuals and health care resources. This community based study was conducted to identify potential predictors of microalbuminuria in a randomly selected sample of adults from the North Central Province (NCP) of Sri Lanka, where the burden of CKD is pronounced and the underlying cause still unknown. Exposures to possible risk factors were determined in randomly recruited subjects (425 females and 461 males) from selected areas of the NCP of Sri Lanka using an interviewer administered questionnaire. Sulphosalicylic acid and the Light Dependent Resister microalbumin gel filtration method was used for initial screening for microalbuminuria and reconfirmed by the Micral strip test. Microalbumnuria was detected in 6.1% of the females and 8.5% of the males. Smoking (p &lt; 0.001), alcohol use (p = 0.003), hypertension...

Objective: The study objective was to validate the use of subjective global assessment (SGA) in assessing the prevalence of malnutrition among patients on hemodialysis in Jordan by comparing SGA grades with anthropometric and biochemical measurements.

marked differences in the pathogenesis, morphology and course of atherosclerosis and arteriosclerosis under the conditions of renal failure have been documented. Among others increased plaque formation and particularly higher proportion and intensity of vascular calcification have been found in clinical and autopsy studies. In addition to the so-called classical or traditional risk factors, an important role for nonclassical risk factors such as microinfl ammation, hyperphosphatemia and oxidative stress has been documented in patients with renal failure and is discussed in detail.

The provision of tertiary paediatric nephrology facilities has led to increasing referrals of children with chronic renal failure (CRF). We report the aetiology and outcomes over 5 years, during which period the improving socio-economic situation has allowed increasing provision of dialysis and transplantation. The records of 205 children (124 male; 60.5%) who were referred to a tertiary paediatric nephrology unit in Khartoum between 2001 and 2006 with a glomerular filtration rate of less than 50 ml/min per 1.73 m 2 body surface area were reviewed. The mean age at the time of diagnosis with CRF was 9.8 years (range 3 months-17 years). The aetiology was chronic glomerulonephritis in 52 (25.4%), congenital urological malformations in 36 (17.5%), urolithiasis in 19 (9.3%), hereditary nephropathy in 14 (6.8%), multisystem diseases in 4 (2%), and cause unknown in 80 (39.1%). Of the 205 children, 136 (63%) had reached end-stage renal failure, with chronic haemodialysis being undertaken in 48 (35.3%), intermittent peritoneal dialysis in 43 (31.6%), continuous ambulatory peritoneal dialysis in 17 (14.7%), and no treatment in 25 (18.4%). At the end of the study period 53 of the 205 (25.9%) remained on dialysis, 51 (25%) were on conservative treatment, 8 (3.9%) had received transplants, 48 (23.4%) had died, and 45 (22%) had been lost to followup. The results illustrate the geographical variations in CRF aetiology in different countries, which may be influenced by current patterns of referral as well as environmental and society factors. The large number with an unknown aetiology for their CRF requires further prospective investigation. We hope the current high mortality rate will improve with earlier referral, improved nutrition, family support, and better access to treatment modalities, especially the provision of kidney transplantation from living related donors.

We present a retrospective study of 30 children of mean age 3.02 ± 1.81 years with steroid-resistant nephrotic syndrome (SRNS) treated with intravenous injection of methylprednisolone plus orally administered prednisone; 24 children also received cyclophosphamide (CP). Sixteen were resistant to steroids from the beginning, and 14 after a mean of 11.26 ± 16.61 months. The initial histological diagnosis was: 18 minimal change disease (MCD), 11 focal segmental glomerulosclerosis (FSGS) and one diffuse mesangial proliferative glomerulonephritis (DMPG). Total remission was achieved in 22 patients (73.3%), partial response in three (10%) and no response in five (16.6%), two of whom were brothers carrying an NPHS2 gene double mutation. There was no difference in response between the MCD and FSGS patients; the only patient with DMPG did not respond. Only initial resistance was a sign of bad prognosis. At follow-up (6.4 ± 3.6 years from last pulse), 21/22 were still in remission, 14/21 were without treatment. Six patients required cyclosporine or mycophenolate mofetil because of steroid dependence. Two non-responders developed end-stage renal failure (ESRF); the remaining patients maintained normal glomerular filtration. The treatment was well tolerated. In conclusion, most of the patients treated with sequential therapy consisting of methylprednisolone (MP) (100%) and CP (80%) showed remission and preserved renal function, but 20% developed steroid dependence.

This paper proposes a novel model-based control methodology for a computer-controlled hemodialysis system, designed to maintain the hemodynamic stability of end-stage renal failure patients undergoing fluid removal during hemodialysis. The first objective of this paper is to introduce a linear parameter varying system to model the hemodynamic response of patients during hemodialysis. Ultrafiltration rate (UFR) and dialysate sodium concentration (DSC) are imposed as the inputs, and the model computes the relative blood volume (RBV), percentage change in heart rate (ΔHR), and systolic blood pressure (SBP) during the course of hemodialysis. The model parameters were estimated based on data collected from 12 patients undergoing 4 profiled hemodialysis sessions. The modeling results demonstrated that the proposed model could be useful for estimating the individual patient's hemodynamic behavior during hemodialysis. Based on the model, the second objective is to implement a computer-controlled hemodialysis system for the regulation of RBV and HR during hemodialysis while maintaining SBP within stable range. The proposed controller is based on a model predictive control approach utilizing pre-defined constraints on the control inputs (UFR and DSC) as well as the output (SBP). The designed control system was experimentally verified on four patients. The results demonstrated that the proposed computer-controlled hemodialysis system regulated the RBV and HR of the patients according to individual reference profiles with an average mean square error of 0.24% and 2.6%, respectively, and thus can be potentially useful for ensuring the stability of patients undergoing hemodialysis by avoiding sudden changes in hemodynamic variables.

Alport syndrome is a hereditary type IV collagen disease leading to progressive renal fibrosis, hearing loss and ocular changes. End stage renal failure usually develops during adolescence. COL4A3−/− mice serve as an animal model for progressive renal scarring in Alport syndrome. The present study evaluates the role of Discoidin Domain Receptor 1 (DDR1) in cell-matrix interaction involved in pathogenesis of Alport syndrome including renal inflammation and fibrosis. DDR1/COL4A3 Double-knockouts were compared to COL4A3−/− mice with 50% or 100% expression of DDR1, wildtype controls and to DDR1−/− COL4A3+/+ controls for over 6 years. Double-knockouts lived 47% longer, mice with 50% DDR1 lived 29% longer and showed improved renal function (reduction in proteinuria and blood urea nitrogen) compared to animals with 100% DDR1 expression. Loss of DDR1 reduced proinflammtory, profibrotic cells via signaling of TGFβ, CTGF, NFκB and IL-6 and decreased deposition of extracellular matrix. Immunogold-staining and in-situ hybridisation identified podocytes as major players in DDR1-mediated fibrosis and inflammation within the kidney. In summary, glomerular epithelial cells (podocytes) express DDR1. Loss of DDR1-expression in the kidney delayed renal fibrosis and inflammation in hereditary type IV collagen disease. This supports our hypothesis that podocyte-matrix interaction via collagen receptors plays an important part in progression of renal fibrosis in Alport disease. The blockade of collagen-receptor DDR1 might serve as an important new therapeutic concept in progressive fibrotic and inflammatory diseases in the future.

Elevated plasma homocysteine, arterial stiffness, and increased pulse pressure (PP) are independently associated with higher cardiovascular risk in patients with end-stage renal disease. The aim of this study is to investigate the influence of plasma homocysteine on arterial stiffness and PP in hemodialysis (HD) patients. One hundred and nine HD patients were stratified into three groups by plasma homocysteine levels: low (11.2-20.8 mol/L), middle (21.2-25.1 mol/L), and high tertiles of plasma homocysteine (Hcy) group (25.2-43.9 mol/L). Using a computerized oscillometry, we measured the arterial stiffness index (ASI) and blood pressure (BP) hemodynamic parameters in the brachial artery. The high Hcy group exhibited a higher ASI (110.4 ± 129.5 versus 46.2 ± 17.5, mean ± S.E., P < 0.01), PP (59.7 ± 23.1 versus 43.3 ± 16.3 mmHg, P < 0.01), and age (57.8 ± 14.1 versus 49.9 ± 12.7 years, P < 0.05) compared with the low Hcy group. Plasma homocysteine was significantly correlated with ASI (r = 0.25, P < 0.001), PP (r = 0.33, P < 0.001), systolic BP (r = 0.31, P < 0.001), and age (r = 0.24, P < 0.05). Serum ferritin was significantly correlated with ASI (r = 0.24, P < 0.05) and PP (r = 0.23, P < 0.05). ASI was also correlated with PP (r = 0.64, P < 0.001). Multiple regression analyses showed that both plasma homocysteine and serum ferritin had significant associations with ASI (β = 4.246, P = 0.007 and β = 0.024, P = 0.006, respectively), and with PP (β = 1.089, P = 0.002 and β = 0.005, P = 0.005, respectively) independent of other classic risk factors for atherosclerosis. In conclusion, plasma homocysteine, along with serum ferritin, may act as an important predictor for arterial stiffness and PP in HD patients.

| Toll-like receptors (TLRs) have a key role in innate immunity. These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue. TLRs mediate signal transduction pathways through the activation of transcription factors that regulate the expression of proinflammatory cytokines and chemokines and are required for the development of adaptive immune responses. TLRs might have an important role in the pathogenesis of renal diseases: their exaggerated activation is associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute tubulointerstitial nephritis, acute renal transplant rejection and delayed allograft function. As the results of previous studies concerning the role of TLRs in renal diseases are conflicting, further work is needed to determine the exact role of these receptors and to evaluate strategies to prevent TLR-mediated local inflammation. This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response.

Background and objectives: Hypertension is a significant cause of chronic renal injury and its effective treatment is capable of reducing the rate of renal failure. b-Adrenoceptor antagonists (b-blockers) have been reported to induce a deterioration in renal function, while several data have indicated a renoprotective effect of treatment with the angiotensin II type 1 receptor antagonist losartan. Previous studies of the interaction between the selective b 1 -blocker bisoprolol and kidney function were performed only for shortand medium-term periods. The aim of this study was to compare the antihypertensive efficacy and renal and cardiac haemodynamic effects of bisoprolol with those of losartan over a 1-year time period in patients with essential hypertension. Methods: Seventy-two patients (40 males) with recently diagnosed uncomplicated (European Society of Hypertension [ESH] criteria stage 1-2) hypertension (mean -SD age 52 -12 years) were enrolled in the study. After a run-in period of 14 days on placebo, the patients were randomized in a double-blind, prospective study to receive either bisoprolol 5 mg or losartan 50 mg, administered once daily for 1 year. At recruitment and 12 months after treatment, cardiac output and renal haemodynamics and function were evaluated by echocardiography and radionuclide studies, respectively. Results: There were no significant differences in baseline clinical data, including glomerular filtration rate and blood pressure, between the two treatment groups. At 1 year, blood pressure had decreased significantly (p < 0.001) with both treatments, and heart rate was reduced only in the group taking bisoprolol. The long-term effects on renal haemodynamics and cardiac function were similar with both drugs, the only change being a significant reduction in the filtration fraction for each group.

Background It is now common for elderly patients with end-stage kidney disease to be offered treatment by dialysis. However, what these patients expect from dialysis is not known. Therefore, the purpose of this study was to elucidate the expectations of elderly patients starting dialysis and to investigate whether their views change after 6 months on this treatment. Methods This was a prospective observational qualitative study of patients commencing haemodialysis in our centre from 2006 to 2007. Data were collected by interview and review of case notes at the time of starting dialysis and after 6 months of treatment. Patients were asked about their expectations from dialysis, symptoms, and views on advance care planning. Results Data were collected from 22 patients (mean age 69.1 years) within a month from starting dialysis. Seventy per cent of these patients had attended a pre-dialysis clinic for at least 4 months previously; despite this, many of the patients complained about having had little choice in starting dialysis and seemed uncertain about what dialysis would involve. Even so, over 90% of those interviewed were optimistic about dialysis, had high expectations from treatment and were not keen to discuss advance care planning at first interview. Sixteen patients were re-interviewed at 6 months (four patients had died meanwhile and two had been transferred to other centres). After 6 months, there was a change in patients’ attitude, with only 45% of them still finding dialysis acceptable and more patients now keen to discuss advance care planning. Symptom burden was higher at 6 months than at initiation of dialysis treatment. Conclusion Most elderly patients have unrealistic expectations from dialysis at the start of treatment. There is a need for more specific counselling of these patients to ensure that they make informed decisions about treatment modality and have realistic expectations if they chose to receive RRT.

Objective: The study objective was to validate the use of subjective global assessment (SGA) in assessing the prevalence of malnutrition among patients on hemodialysis in Jordan by comparing SGA grades with anthropometric and biochemical measurements.

Intravenous iron (Fe) and recombinant human erythropoietin (rHuEPO) are routine treatments in the management of anemia in patients with chronic renal failure. We investigated the oxidative stress acutely induced by these therapies and whether pretreatment with oral melatonin (MEL) would have a beneficial effect. Nine patient s (four women) were studied within I month of entering a chronic hemodialysis program in the interdialytic period. Plasma malondialdehyde (MDA), red blood cell glutathione (GSH), and catalase (CAT) activity were measured in blood samples obtained before (baseline) and 1, 3, and 24 hours after the administration of Fe (100 mg of Fe saccharate intravenously over 1 hour) or rHuEPO (4,000 U intravenously). One hour before these treatments, patients were administered a single oral dose of MEL (0.3 mg/kg) or placebo. Each patient was studied on four occasions, corresponding to studies performed using either placebo or MELin association with intravenous Fe and rHuEPO administration. Baseline data showed increased oxidative stress in patients with end-stage renal failure. Increments in oxidative stress induced by Fe were more pronounced at the end of the administration: MDA, baseline, 0.74 -+ 0.09 nmol/mL; 1 hour, 1.50 _+ 0.28 nmol/mL (P < 0.001); GSH, baseline, 2.51 -+ 0.34 nmol/mg of hemoglobin (Hb); 1 hour, 1.66 +-0.01 nmol/mg Hb (P < 0.001); and CAT activity, baseline, 27.0 _+ 5.7 Mmg Hb; 1 hour, 23.3 -+ 4.2 K/mg Hb (P < 0.001). rHuEPO-induced increments in oxidative stress were more pronounced (P < 0.001) at 3 hours (MDA, 1.24 +_-0.34 nmol/mL; GSH, 1.52 +-0.23 nmol/mg Hb; CAT activity, 18.0 -+ 3.1 Mmg Hb). MEL administration prevented the changes induced by Fe and rHuEPO and had no adverse side effects. These studies show that intravenous Fe and rHuEPO in doses commonly used to treat anemia in chronic hemodialysis patients acutely generate significant oxidative stress. Oral MEL prevents such oxidative stress and may be of clinical use.

The Western Australian Health Services Research Linked Database was used to examine trends in the incidence rate and prevalence of end-stage renal failure and to describe treatment patterns in these patients. Linked hospital morbidity and mortality records from 1980 to 1994 were selected if a record had a principal diagnosis or procedure of chronic renal failure, dialysis, or renal transplantation. Patient records were grouped according to the stage of care (predialysis, dialysis, transplant, or death). A total of 1,046 patients with a principal diagnosis or procedure that met our criteria for end-stage renal failure was admitted to the hospital from 1985 to 1994. Trends in the incidence rate and prevalence of end-stage renal failure by sex and race, patterns of care, indices of comorbidity, and waiting time to transplantation were calculated. Results showed that both the incidence rate and prevalence of end-stage renal failure increased from 1986 to 1994, most noticeably in the aboriginal population. Rates of renal failure in 1994 were 15 times greater in aborigines than in nonaborigines. Of the hospital patients, 73.5% received dialysis three times a week. Complications associated with dialysis treatment were the most common cause of comorbid hospitalization. The mean waiting time to transplantation was 503 days for those who had a transplant and 6.3 years for all patients. The escalating numbers of patients undergoing renal dialysis, the high cost of maintaining them on dialysis, and the additional use of hospital services for comorbid conditions highlight the need to develop programs to prevent the occurrence of renal failure, particularly in the aboriginal population.

The increased effect of arterial wave reflections on central arteries like the common carotid artery seen in end-stage renal failure (ESRF) patients favors myocardial hypertrophy and oxygen consumption and alters coronary blood flow distribution. Nevertheless, the impact of wave reflection on the outcome and end points such as mortality remains to be demonstrated. One hundred eighty ESRF patients (age, 54616

Chronic kidney disease (CKD), a major worldwide public-health problem which affects about 10% of the population, has an increased annual incidence rate of about 5-8%. This increased incidence is mainly due to type 2 diabetes and hypertension and the increasing incidence of elderly patients with CKD. Although the progression to end-stage renal failure (ESRF) is mainly based upon the underlying disease, comorbid conditions such as an initial low renal function, severe proteinuria, and high levels of blood pressure also play important roles in the development of ESRF. Since experimental and clinical evidence suggest that angiotensin II plays a central role in the progression of CKD, pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists has been suggested as firstline treatment for hypertension and prevention of ESRF in these patients. Aliskiren, a novel renin inhibitor is also a promising medical intervention. However, independently of the category of the drugs used, low target blood pressure levels seem to be equally or more important for the delay or prevention of CKD. In this review the results of studies with pharmacological inhibition of the RAAS in patients with diabetic and nondiabetic nephropathy is discussed.

Heart disease and stroke are the first and third leading causes of death, respectively, in the USA 1 . Although the percentage of hypertensive patients receiving treatment has increased, and blood pressure is now better controlled, the incidence of end-stage renal disease and the prevalence of heart failure continue to increase 2 . This suggests that blood pressure reduction alone is not sufficient to prevent end-organ damage and that the additional control of local and/or hormonal factors might be essential. Abnormal activation of the renin-angiotensin-aldosterone system (RAAS) correlates directly with the incidence and extent of endorgan damage 3,4 . Moreover, numerous clinical and experimental studies have demonstrated that blockade of the RAAS with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists provides significant cardiovascular protection 5-9 . Therefore, it has been proposed that overactivation of the RAAS represents a cardiovascular risk factor 10 .

Bullous dermatoses (BD) are well recognized in patients with end-stage renal disease (ESRD). It is important to distinguish pseudoporphyria (porphyrin accumulation due to decreased clearance) from true porphyrias, particularly those in which acute neurological attacks may occur. Investigation of the dialysis patient poses practical diagnostic difficulties because urinary porphyrin profiles are not available. We describe a patient on continuous ambulatory peritoneal dialysis (CAPD) with several recognized causative factors for porphyria cutanea tarda (PCT). The patient presented with a blistering photosensitive rash. We highlight the importance of investigating anuric patients with fractionation of both fecal and plasma porphyrins. Plasma porphyrins were grossly elevated (345 nmol/L; reference range, F13), whereas plasma porphyrins in a control group of CAPD patients without blistering rashes were only minimally elevated (mean, 23.9 nmol/L; SD, 11.0; n ‫؍‬ 9). Fractionation of fecal porphyrins by high-performance liquid chromatography (HPLC) yielded a pattern typical of PCT. In addition to the contributory factors for PCT that were present, it is possible that porphyrin accumulation secondary to renal failure played a role in the expression of her disease. Patients with ESRD presenting with BD require careful evaluation, including fractionation of fecal porphyrins.

Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t1/2) of 2 to 3 hr in subjects with normal renal function. To determine the drug's kinetics and tolerance in patients with severe renal failure, six anuric subjects on long-term hemodialysis were studied. Each received a 1-hr infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a two-compartment open model. ACV terminal plasma t1/2 and the total body clearance were 19.5 ± 5.9 hr ± SD) and 28.6 ± 9.5 ml/min/1.73 012. Peak (end of infusion) and 8-and 24-hr plasma ACV concentrations were 37.5 ± 23.3, 10.3 ± 2.9, and 6.4 ± 2.4

| Toll-like receptors (TLRs) have a key role in innate immunity. These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue. TLRs mediate signal transduction pathways through the activation of transcription factors that regulate the expression of proinflammatory cytokines and chemokines and are required for the development of adaptive immune responses. TLRs might have an important role in the pathogenesis of renal diseases: their exaggerated activation is associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute tubulointerstitial nephritis, acute renal transplant rejection and delayed allograft function. As the results of previous studies concerning the role of TLRs in renal diseases are conflicting, further work is needed to determine the exact role of these receptors and to evaluate strategies to prevent TLR-mediated local inflammation. This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response.

Background: Hemorrhagic stroke and ischemic heart disease continue to be key problems in patients with end stage renal failure. Reduced serum paraoxonase (PON-1) activity has been described in these patients, which could contribute to the accelerated development of atherosclerosis. We hypothesized that retention of uremic toxins and or "middle molecules" including advanced glycation (AGE) free adducts and peptides could play a mechanistic role in decreasing PON-1 activity. Methods: We enrolled 22 ESRD patients undergoing hemodialysis in whom paired pre-and post-dialysis samples were studied along with 30 agematched control subjects. Results: ESRD patients showed a 76% decrease in PON-1 activity. As expected, ESRD patients had an increase in lipoperoxides and advanced oxidation protein products (AOPP). Our patients had a 3-fold increase in serum AGEs and a striking 10-fold increase in low molecular weight (b 10 kDa) AGEs. Post-dialysis samples in all patients displayed an increase in PON-1 activity, which ranged from 4 to 40% of the predialysis value. HDL-cholesterol, apoAI, free cholesterol (as a LCAT surrogate), HDL-subclasses and TG did not change significantly after dialysis. Changes in PON-1 activity display a good correlation (r =0.66, p b 0.001) with rates in which creatinine and urea are cleared. Clearance of low molecular weight AGEs after hemodialysis explains 79% of the changes in PON-1 activity and are hence a much better predictor than creatinine changes (r = 0.89, p b 0.00). In vitro incubation of paraoxonase with serum ultrafiltrates show a time and concentration dependent inhibition of PON-1 by the ultrafiltrates, an inhibition that is up to 3 times higher (from 8 to 24%) when chronic renal failure patients are the source of the ultrafiltrate. Conclusion: We showed that HD results in a significant, consistent increase in the activity of the antioxidant enzyme PON-1. The effect, correlates with the effectiveness of dialysis to clear creatinine and urea, and with the clearance of AGE adducts of low molecular weight. This effect was replicated in vitro, showing time and dose dependency. Our results suggest that another cause for the observed lower PON-1 concentrations in CRF are the retention of low-middle molecules and demonstrate a positive effect of hemodialysis in the delicate oxidant-antioxidant state of these patients, that should be weighted against other pro-oxidant effects that have also been shown to occur previously. If the hypothesis that AGEs are the main culprits is proved in further research, this opens a putative therapeutic avenue for AGE blockers in ESRD.

Introduction Sepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients. Methods Patient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT. Results Among the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patient's propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05). Conclusions Use of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.

The recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation has a potentially detrimental course toward the loss of renal function. To identify prognostic markers for recurrence and efficacy of treatment, we evaluated the outcome of 32 renal allografts in 29 pediatric patients with FSGS who underwent transplantation from 1987 to 1998 in the North Italy Transplant program. Recurrence was observed in 15 of 29 patients (52%) after the first transplant and in 3 of 3 patients (100%) after the second graft. No significant differences in sex, age at FSGS onset, age at transplantation, or length of dialysis were noted between patients with recurrent and nonrecurrent FSGS. Those with recurrence originally developed end-stage renal failure faster (3.9 years) than those without recurrence (6.2 years). Pretransplantation serum samples from 25 patients were tested in an in vitro assay that evaluates glomerular permeability to albumin. FSGS recurred in 11 of 13 children who tested positive for the permeability factor and in 4 of 12 patients with a negative test result; the odds ratio for developing recurrence was 10.99 (95% confidence limit, 1.6 to 75.47) in the former group. The immediate onset of proteinuria after transplantation was a negative prognostic factor for the outcome; 6 of 9 patients in whom proteinuria appeared within 2 days of transplantation returned to dialysis in less than 24 months. In 9 of 11 patients who were treated with plasmapheresis plus cyclophosphamide after recurrence, proteinuria was successfully reversed and persistent remission was obtained in 7 patients. These data show that the glomerular permeability test has a significant predictive value for the recurrence of proteinuria in children with FSGS who have received a renal allograft. Of the clinical parameters considered, only the duration of disease was significantly different in patients with recurrent versus nonrecurrent FSGS. Treatment with plasmapheresis plus cyclophosphamide can be effective in the control of FSGS relapse after renal transplantation.

Background: Autosomal dominant polycystic kidney disease (ADPKD) ranks among the most common genetic disorders. The development of end-stage renal failure usually is after the fourth decade of life. Angiotensinconverting enzyme (ACE) inhibitors often are used as agents to slow the progression of renal failure, although their effectiveness and starting point in ADPKD remain unclear. Methods: We measured technetium 99m diethylenetriamine pentaacetic acid glomerular filtration rate (GFR) and serum cystatin C (Cys-C) levels in 18 children with ADPKD and 41 control patients. Data are given as mean ؎ SD. Mean age was 9.8 ؎ 5.9 years, mean height was 137.5 ؎ 34.3 cm, and mean weight was 39.2 ؎ 22.8 kg in the ADPKD group, not significantly different from controls, with an average age of 10.4 ؎ 4.9 years, height of 138.0 ؎ 26.1 cm, and weight of 38.0 ؎ 16.8 kg. Results: Mean serum creatinine levels did not differ between the ADPKD (0.6 ؎ 0.2 mg/dL [51.1 ؎ 20.4 mol/L]) and control groups (0.7 ؎ 0.2 mg/dL [59.8 ؎ 15.3 mol/L]; P ‫؍‬ 0.19)