Main Cause Of Renal Failure Research Articles

Cross-species single-cell analysis uncovers the immunopathological mechanisms associated with IgA nephropathy progression.

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Serum Ferritin Reflects Bone Marrow Iron Stores in Children with End Stage Kidney Disease

Background: Iron deficiency is common in children with end-stage kidney disease (ESKD) but diagnosing iron deficiency in ESKD is challenging as serum indicators of iron stores may be influenced by inflammation and other factors. We examined which of the clinically used serum iron indices were predictive of bone marrow iron stores (the gold standard) in dialysis-dependent children and young adults with ESKD, in the setting of increased nutritional requirements and co-existing inflammation. Methods: This cross-sectional study enrolled 71 clinically-stable children and young adults (age range 2 to 28 years) receiving dialysis, who underwent bone biopsy for CKD-mineral bone disorders between 2007 through 2011. Congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary diseases (63.3%) were the main causes of renal failure, followed by primary glomerulonephritis (36.7%). Bone samples were stained with Perls' Prussian blue and independently interpreted by a pathologist unaware of the patients' iron parameters and clinical status. Staining was scored absent vs present for receiver operator curve (ROC) analysis. In ROC analysis, the ability of serum ferritin to predict bone sample iron stores was compared with serum hepcidin, transferrin saturation (TSAT), and clinical guideline-based iron deficiency cut-offs for serum iron, TSAT, and their combination. We generated optimal cut off points using the Youden's J statistic. Results: Mean age was 17.2 ± 4.4 years, and 30% of subjects were female. Median dialysis vintage was 1.2 (IQR 0.7, 2.0) years, and 56% were supported by peritoneal dialysis. Mean hemoglobin was 12.4 ± 1.7 g/dl, and 35% were receiving iron supplementation at the time of biopsy. Based on gold standard of depleted bone iron stores, 46.5% patients were iron-deficient. As a predictor of bone marrow iron staining, serum ferritin provided the highest area under the ROC curve compared to other tests (Table), but at the usual clinical ferritin cutoff (100 ng/ml) only 22% of true iron-deficient subjects were diagnosed compared to 52% of true iron-deficient subjects using a higher optimal cutoff point for ferritin (188 ng/ml). Conclusions: In children with ESKD, iron deficiency as determined by the gold standard bone iron staining was highly prevalent (close to 50%), and serum ferritin provided the best prediction of bone sample iron stores. Optimal ferritin cutoff for decision-making about iron administration should reflect the current relative risks and benefits of iron therapy. Future trials testing higher ferritin cut-offs and patient centered outcomes in children with ESKD are timely.

Integrated multiple-microarray analysis and mendelian randomization to identify novel targets involved in diabetic nephropathy.

Diabetic nephropathy (DN), which is the main cause of renal failure in end-stage renal disease, is becoming a common chronic renal disease worldwide. Mendelian randomization (MR) is a genetic tool that is widely used to minimize confounding and reverse causation when identifying the causal effects of complex traits. In this study, we conducted an integrated multiple microarray analysis and large-scale plasma proteome MR analysis to identify candidate biomarkers and evaluate the causal effects of prospective therapeutic targets in DN. Five DN gene expression datasets were selected from the Gene Expression Omnibus. The robust rank aggregation (RRA) method was used to integrate differentially expressed genes (DEGs) of glomerular samples between patients with DN and controls, followed by functional enrichment analysis. Protein quantitative trait loci were incorporated from seven different proteomic genome-wide association studies, and genetic association data on DN were obtained from FinnGen (3676 cases and 283,456 controls) for two-sample MR analysis. External validation and clinical correlation were also conducted. A total of 82 DEGs (53 upregulated and 29 downregulated) were identified through RRA integrated analysis. The enriched Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathways of the DEGs were significantly enriched in neutrophil degranulation, neutrophil activation, proteoglycan binding, collagen binding, secretory granule lumen, gluconeogenesis, tricarboxylic acid cycle, and pentose phosphate pathways. MR analysis revealed that the genetically predicted levels of MHC class I polypeptide-related sequence B (MICB), granzyme A (GZMA), cathepsin S (CTSS), chloride intracellular channel protein 5, and ficolin-1 (FCN1) were causally associated with DN risk. Expression validation and clinical correlation analysis showed that MICB, GZMA, FCN1, and insulin-like growth factor 1 may participate in the development of DN, and carbonic anhydrase 2 and lipoprotein lipase may play protective roles in patients with DN. Our integrated analysis identified novel biomarkers, including MICB and GZMA, which may help further understand the complicated mechanisms of DN and identify new target pathways for intervention.

Targeted-release budesonide in immunoglobulin A nephropathy; a mini-review

Immunoglobulin A nephropathy is the most common kind of primary glomerulonephritis worldwide and one of the main causes of renal failure. Systemic corticosteroid therapy may protect against renal deterioration in IgA nephropathy; however, it is not often advised for long-term treatment due to possible side effects. Recent studies present promising results of the new targeted-release formulation of budesonide that delivers the drug to the distal ileum to reduce side effects for patients with IgA nephropathy. In this paper, we highlighted the potential benefits of budesonide as a treatment option for IgA nephropathy and the need for additional studies to confirm its effectiveness. The lack of alternative treatments to prevent renal deterioration without other systemic side effects motivated us to gather relevant information to fill this gap. In this brief overview, we have reviewed some of the most recently published studies regarding how budesonide protects against IgA nephropathy. Studies reveal that budesonide might significantly decrease proteinuria, hematuria, and creatinine level while maintaining normal renal function. Though, a limited number of trials have been established to date, and further investigations are needed to confirm the benefit of the new targeted-release budesonide in treating IgA nephropathy.

SIRT1-SIRT7 in Diabetic Kidney Disease: Biological Functions and Molecular Mechanisms.

Diabetic kidney disease (DKD) is a severe microvascular complication in patients with diabetes and is one of the main causes of renal failure. The current clinical treatment methods for DKD are not completely effective, and further exploration of the molecular mechanisms underlying the pathology of DKD is necessary to improve and promote the treatment strategy. Sirtuins are class III histone deacetylases, which play an important role in many biological functions, including DNA repair, apoptosis, cell cycle, oxidative stress, mitochondrial function, energy metabolism, lifespan, and aging. In the last decade, research on sirtuins and DKD has gained increasing attention, and it is important to summarize the relationship between DKD and sirtuins to increase the awareness of DKD and improve the cure rates. We have found that miRNAs, lncRNAs, compounds, or drugs that up-regulate the activity and expression of sirtuins play protective roles in renal function. Therefore, in this review, we summarize the biological functions, molecular targets, mechanisms, and signaling pathways of SIRT1–SIRT7 in DKD models. Existing research has shown that sirtuins have the potential as effective targets for the clinical treatment of DKD. This review aims to lay a solid foundation for clinical research and provide a theoretical basis to slow the development of DKD in patients.

POS-357 CAMP-RESPONSE ELEMENT BINDING PROTEIN MEDIATES PODOCYTE INJURY IN DIABETIC NEPHROPATHY BY TARGETING LNCRNA DLX6-AS1

Diabetic nephropathy (DN) is one of the most severe microvascular complications of diabetic mellitus, and main cause of renal failure in patients with end-stage renal disease. In our previous study, lncRNA DLX6-AS1 (DLX6-AS1, Dlx6-os1 in mice) was found to be associated with the extent of albuminuria in DN patients. Furthermore, the lack of Dlx6-os1 was pivotal in switching off the inflammatory response in a diabetic mouse model. However, the regulatory factors responsible for elevated DLX6-AS1 in DN remains unknown.

Ретроспективный анализ течения, подходов к диагностике и терапии типичного и атипичного гемолитико-уремического синдрома у детей в Тюменской области

Being one of the main causes of renal failure in children, hemolytic uremic syndrome (HUS) is a significant therapeutic challenge for pediatricians. Limited epidemiological data on the incidence and prevalence of HUS in the pediatric population suggests the need for studies in this area. Objective. To assess specific clinical characteristics of HUS in children residing in Tyumen region, analyze diagnostic approach used in this region, and identify the main effective therapeutic regimens. Materials and methods. We performed retrospective analysis of 33 HUS cases. In the majority of them, symptoms of acute renal failure were preceded by an episode of diarrhea with hemocolitis, while their disease progression manifested with extrarenal complications involving the cardiovascular system, nervous systems, and gastrointestinal tract. Laboratory testing demonstrated signs typical of thrombotic microangiopathy, which is considered as an underlying pathological mechanism of HUS: Coombs-negative hemolytic anemia, thrombocytopenia. Acute kidney damage was confirmed by hyperazotemia and proteinuria. Differential diagnosis of typical and atypical HUS was based on the measurement of ADAMTS-13 level and testing for Shiga toxin. Results. Instrumental examinations confirmed renal failure and extrarenal complications. In the majority of patients, first-line therapy included renal replacement therapy, plasma transfusion, and hemotransfusion. Patients with verified atypical HUS received the complement inhibitor Eculizumab. Since new diagnostic tests are not available everywhere, it is necessary to consider an organizational decision regarding testing according to indications activity ADAMTS-13 and the administration of complement-inhibiting drugs as first-line therapy for atypical HUS. Key words: hemolytic uremic syndrome, dialysis, monoclonal antibodies, renal failure, ADAMTS-13

Is screening of Staghorn Stones cost-effective?

Staghorn stones can cause damage to the kidneys and are considered as the one of the main cause of renal failure. If they are identified during the initial stages of diagnosis, kidney damage can be prevented. Screening can lead to a better diagnosis. Before the screening, it is necessary to calculate the cost-effectiveness of screening. Using the possibility calculations of staghorn stones in the society and different age groups as well as a decision tree model, the screening costs and effectiveness were calculated against no screening. Effectiveness was determined based on the number of prevented cases of renal failure. Ultimately, the incremental cost-effectiveness ration (ICER) was calculated and compared with the World Health Organization (WHO) method based on the gross domestic product (GDP) per capita and subgroup analysis was done for different age groups. In addition, the robustness of results was examined by sensitivity analysis. The results of decision tree showed that in the screening group, the expected cost was 8815997 USD and the expected effectiveness was 358 and in the no-screening group, the expected cost was 3954214 USD and the expected effectiveness was 258. Based on the results of the study, screening compared with no screening would increase the cost by 4861783 USD and effectiveness would increase by 100 people. The incremental cost-effectiveness ratio (ICER) showed that for each unit of increase in effectiveness of screening compared with no screening, would lead to an increase the cost by 48618 USD. The results also indicated that screening 30-70-year-old people compared with other age groups (20-70 and 25-70) if done every two years, could reduce the mean costs per preventing each case of renal failure.Conclusion: If screening staghorn stones are done every two years for 30-70-year-old individuals, it would be cost effective considering WHO method and 3026 USD could be saved in the health care system per each person.

MicroRNA29-a as Diabetic Nephropathy Biomarker in Diabetic Patients (Type 2)

AbstractBackground: Diabetic nephropathy (DN) is one of the main causes of renal failure. Recent research demonstrated that the serial microbes (miRNA) could be used as a marker to detect pathogenic disease; the DN-related miRNAs could not be studied.Aim of Study: In this study the aim was to investigate the predictive value of miRNA29-a in diabetes mellitus type 2 (T2DM) patients in relation to nephropathy risk onset predic-tion.Subjects and Methods: In the present study a total of (120) persons were divided into three groups as Group (I): (N=20) control group, Group (II): (N=50) T2DM patients without renal symptoms Group (III): (N=50) T2DM patients with renal insufficiency, RT-PCR method was used to determine the relative quantitative of miRNA29-a.Results: Increased levels of HbA1c, FBS, urea, creatinine and Albumin/creatinine ratio (ACR) were observed in subjects under study.An increased levels of miRNA 29-a in group III, DN (51.97-}61.78) and group II, DM (7.06±6.83) when com-pared with group I, control subjects (0.8-}0.2). The result of the present study implied that miRNA 29-a could be served as an early indicator of DM-mediated renal pathogenesis.

RELATIONSHIP BETWEEN NEUTROPHIL - LYMPHOCYTE RATIO AND DECREASED GLOMERULAR FILTRATION RATE IN DIABETIC NEPHROPATHY

Diabetic nephropathy is one of the fairly severe Diabetes Mellitus (DM) complications and the main cause of renal failure that can result in mortality. Hyperglycemia in DM induces kidney injury that may result in hemodynamic and metabolic alterations, endothelial dysfunction and inflammatory cells activation. A persistent and continuous inflammation is observed in diabetic nephropathy. One of the inflammation process progression indicators is Neutrophil-Lymphocyte Ratio (NLR). To find out the relationship between NLR and decreased Glomerular Filtration Rate (GFR) in diabetic nephropathy. This study was an observational study with a retrospective approach. This study was conducted in Clinical Pathology Laboratory Installation and Medical Record Installation of Dr. Wahidin Sudirohusodo Makassar Hospital by collecting the patient's data during February 2015 to February 2016. Patients that were diagnosed as type 2 DM without diabetic nephropathy complication were taken as control and those diagnosed as type 2 DM with diabetic nephropathy were treated as study subjects. One hundred and thirteen (113) samples met the inclusion criteria, consisting of 73 diabetic nephropathy patients with Chronic Kidney Disease (CKD) 13 diabetic nephropathy patients without CKD and 27 type 2 DM patients without diabetic nephropathy complication. Patients consisted of 57 males (50.4%) and 56 females (49,6%). Neutrophil-lymphocyte ratio and GFR values in the group of diabetic nephropathy without CKD were 2.03±0.68 and 85.38±24.63, respectively. Whereas, the NLR and GFR values in control group were 1.74±0.54 and 90.03±28.60, respectively. In the group of diabetic nephropathy with CKD, NLR value increased by 3.19±1.83 and GFR decrease by 30.54±16.45. Spearman test indicated a significant relationship between NLR increase and decreased GFR (r = -0.635, p=0.00). There is a significant relationship between NLR increase and decreased GFR in patients with diabetic nephropathy.

Hemodiálisis en Pacientes con Mieloma Múltiple: a propósito de dos casos

El Mieloma múltiple es una patología hematológica en la que existe una proliferación de células plasmáticas a nivel de la médula ósea, causan un exceso de producción de cadenas ligeras, la presencia de estas cadenas ligeras libres incompletas es la causa principal de insuficiencia renal. Caso clínico: Presentamos dos casos de pacientes de 56 y 73 años con mieloma múltiple con cadenas Lambda y Kappa y con fracaso renal agudo. Fueron tratados en la unidad de diálisis del Hospital Rey Juan Carlos con hemodiálisis largas utilizando el filtro Filtryzer BK-2.1F®. Ambos precisaron de terapia combinada de quimioterapia y hemodiálisis largas y diarias con dializador de poro ancho. Se apreció que con las sesiones de hemodiálisis las cadenas ligeras disminuyeron considerablemente y que los dos pacientes mejoraron el filtrado glomerular sin precisar sesiones de hemodiálisis. La complicación más frecuente fue la coagulación del circuito extracorpóreo. Se resalta la importancia iniciar un diagnóstico y tratamiento precoz para reducir el riesgo de insuficiencia renal crónica.

An effect of combination of resveratrol with vitamin D3 on modulation of proinflammatory cytokines in diabetic nephropathy induces rat

Diabetic nephropathy is the one of the major complication of diabetes mellitus which is the main cause of renal failure. The treatment of diabetic nephropathy includes different nonpharmacological and pharmacological approach, but poor prognosis. Our study was designed to investigate the combined effect of resveratrol and vitamin D3 on the glucose homeostasis, histological changes, and cell damage biomarkers in streptozotocin-induced diabetic rat kidneys. Oral treatment with resveratrol (10 mg/kg/day), vitamin D3 (0.5 µgm/kg), and the combination for 10 weeks showed an increase in the average body weights compared to the untreated diabetic rats. The combination showed a highly significant decrease in fasting blood glucose levels, serum cholesterol levels compared to the untreated diabetic rats, there is a significant increase in serum HDL cholesterol levels. There is a highly significant decrease in serum creatinine, urea, albumin levels compared to the untreated diabetic rats. However, the combination treatment provides superior efficacy than individual drug treatments. Histopathological examination of the kidney tissue section revealed that the diabetic rats treated with resveratrol, vitamin D3, and the combination showed noticeable improvement in the histopathological parameters compared to untreated diabetic rats. However, a marked reduction of TNF-α and IL-6 expression was observed in combination treated rats compared to individual drug treatments. Combination therapy was significantly more effective in treating diabetic nephropathy than resveratrol and vitamin D3 alone. Resveratrol and vitamin D3 has a protective role of diabetic kidneys.

Dialysis in adults in year 2000 in the Republic of Macedonia.

1,019 adult patients with terminal renal failure were treated with dialysis (D) in the first part of the year 2000 in the Republic of Macedonia. 1,010 patients (99%) were treated with chronic intermittent (maintenance) hemodialysis (HD) while nine patients (1%) were on continuous ambulatory peritoneal dialysis (CAPD). For the children, a special peritoneal dialysis program was developed; 509 patients per million of the population (PMP) were on dialysis. The Republic of Macedonia is, therefore, among those central and eastern European countries with a higher PMP number in the treatment of end-stage renal disease, following Croatia, the Czech Republic and Slovenia. The patients were treated at 18 Centers in a network of HD Centers at a distance of 30-50 km. from their place of residence in order to facilitate their access to treatment and to work. All patients who have had symptoms indicating need for treatment with D were accepted for treatment. The government payed all the expenses of the treatment and the salaries of the staff. 56% were male and 44% were female patients. The youngest patient was aged 9 and the oldest was 82 years old. There has been an increase in the age of the patients on D as well as an increase in their number. In 1993 we had 727 patients being treated with D, and now we have 1,019 with a constant increase in the number of patients with ESRD and a need for D and renal transplantation. Mortality per year at the different Centers ranged from 8-19% in 1999 and the average is 12%. Glomerulonephritis (GN)--both primary and secondary--is the main cause of renal failure (RF) in some Centers up to 45%. Tubulo-interstitial disease follows GN. ADPKD patients constitute 9.4% with a difference among the Centers of 3-29%, and diabetic nephropathy is found in 10%, 5-15% in different Centers. 11-61% of patients have an unknown etiology. 352 patients are on treatment with human recombinant erythropoietin (rhuEPO) - in some Centers up to 60%. The mode of application was subcutaneous and the initial dose is 20 U/kg body weight and the mean maintenance dose of EPO per patient weekly is 4,000 U. The Cimino-Brescia arteriovenous fistula is being applied as a standard vascular access. The survival rate of our patients treated with maintenance HD at 5 years was 58%. CAPD and particularly renal transplantation are to be further developed as alternative methods in treating terminal renal failure.

Sleeve Gastrectomy after Renal Transplantation.

Obesity induces or accelerates diabetes (DBT), hypertension (HT), and dyslipidemia (DSL), which are the main causes of renal failure. Obesity exacerbates in patients after renal transplantation (RT), and it has been associated with increased mortality rate, postoperative complications, and graft loss. We hypothesize that bariatric surgery might have a positive effect on obese patients with history of previous RT. This was a retrospective review from prospectively collected data. Patients with sleeve gastrectomy (SG) with history of RT were studied. Demographics, anthropometric data, effect on comorbidities, postoperative course, immunosuppressive treatment, reason for transplantation, kidney function, graft survival, and quality of life associated with SG in obese patients with previous RT were assessed using a survey. From January 1, 2012 to January 1, 2016, five kidney transplant patients were operated on; 80% were female, with an average preoperative BMI of 42.18 ± 8.5kg/m2 (range 37-54). Related comorbidities: 100% of the patients had HT and DSL, whereas 40% had DBT and gout. The average time gap between RT and SG was 15 ± 8.4years (range 3-22). Average operative time was 65 ± 12min (range 60-85), and there were neither complications nor mortality. At 16.8 ± 14.5months (range 5-46) of follow-up, BMI was 29.8 ± 7.3kg/m2 (range 26-44). All patients with HT and DSL were able to decrease their medication, showing improvement in blood pressure levels and laboratory test values. Regarding DBT, insulin was discontinued in one case, limiting the treatment to the use of oral hypoglycemic agents only. In another case, insulin dosage was significantly reduced. Graft function and proteinuria level improved in 80% of patients. All patients experienced a significant improvement in their quality of life. In this specific group of high-risk patients, SG showed encouraging results in terms of weight loss and resolution/improvement of comorbidities, renal function, and quality of life.

A Comparative Study between Dialysis and Kidney Transplantation regarding the Causes and Survival Period of the Patients in Western Area , Libya

As the number of renal failure patients in Libya reached to 3,700 patients (kindly provided by Libyan Ministry of Health), this study aimed to help Libyan people suffering from renal failure to making a wisdom decision about choice of renal transplantation or treatment with dialysis. This study found the main causes of renal failure among people in western area of Lib- ya, due to ages and survival time between patient undergoing dialysis and kidney transplantation. Out of 140 patients' files that were collected from different hospital and specialized centers in western Libya, 98(70%) patients were treated with dialysis while the rest 42 patients (30%) underwent kidney transplantation. The result also revealed that the mean survival time for those who planted the kidneys was (7.1 years) significantly longer than those treated with dialysis (3.7 years). The mean ages of patients underwent transplantation was (53.4 years) younger than those who were treated with dialysis (44.6). Diabetes and blood pressure complications were the most common diseases associated among both groups while multiple microbial inflammation of kidney was higher among kidney. transplanted group. Also, gastrointestinal bacteria and protozoa played a marked role.

A COMPARATIVE STUDY BETWEEN DIALYSIS AND KIDNEY TRANSPLANTATION REGARDING THE CAUSES AND SURVIVAL PERIOD OF THE PATIENTS IN WESTERN AREA, LIBYA

As the number of renal failure patients in Libya reached to 3,700 patients (kindly provided by Libyan Ministry of Health), this study aimed to help Libyan people suffering from renal failure to making a wisdom decision about choice of renal transplantation or treatment with dialysis. This study found the main causes of renal failure among people in western area of Lib- ya, due to ages and survival time between patient undergoing dialysis and kidney transplantation. Out of 140 patients' files that were collected from different hospital and specialized centers in western Libya, 98(70%) patients were treated with dialysis while the rest 42 patients (30%) underwent kidney transplantation. The result also revealed that the mean survival time for those who planted the kidneys was (7.1 years) significantly longer than those treated with dialysis (3.7 years). The mean ages of patients underwent transplantation was (53.4 years) younger than those who were treated with dialysis (44.6). Diabetes and blood pressure complications were the most common diseases associated among both groups while multiple microbial inflammation of kidney was higher among kidney. transplanted group. Also, gastrointestinal bacteria and protozoa played a marked role.

Preventive role of estradiol on kidney injury induced by renal ischemia-reperfusion in male and female rats.

Background:Renal ischemia-reperfusion (RIR) is the main cause of renal failure. The incidence of RIR injury seems to be gender-related due to female sex hormone; estrogen. This study was designed to investigate the protective role of estrogen against RIR injury in male and ovariectomized female rats.Methods:Thirty-nine Wistar rats were used in this study as male and ovariectomized female rats in the sham-operated, RIR, and estradiol-treated plus RIR groups. The RIR was induced by clamping the renal vessels for 45 min and then 24 h of reperfusion. All animals finally were sacrificed for the measurements.Results:The serum levels of creatinine and blood urea nitrogen and kidney tissue damage score significantly increased in both male and female RIR rats (P < 0.05). Estradiol however significantly attenuated theses parameters (P < 0.05) toward normal levels in female (P < 0.05), but not in male rats. Kidney weight increased in both genders and estradiol intensified it in the male rats (P < 0.05). Uterus weight was increased by estradiol in female rats (P < 0.05) and testis weight did not alter in male rats.Conclusions:Estradiol demonstrated a protective role against RIR injury in female rats; however, estradiol as an antioxidant could not protect the male kidney from RIR injury.

Intoxicação por carambola em paciente com insuficiência renal crônica: relato de caso

Chronic renal failure is a high morbidity and mortality condition, with its terminal phase incidence and prevalence steadily growing year after year. According to the Sociedade Brasileira de Nefrologia [Brazilian Society of Nephrology], the main causes of renal failure are arterial hypertension, glomerulonephritis and diabetes mellitus. Several factors are implied on chronic renal failure patients' risk of mortality, particularly age, diabetes and associated co-morbidities. For patients below 50 years old, the 5 years survival rate is 62% and for those above this age and with diabetes mellitus, just 23%. Star fruit is native from Asia, and widespread in tropical countries; this fruit was reported as having a neurotoxin able to cause serious neurological changes in chronic renal disease patients. These may range from mild features, such as hiccup and confusion, to serious episodes with seizures and death. This neurotoxin apparently inhibits specifically the GABAergic conduction system. This paper describes a case involving a chronic renal disease patient who, after ingesting star fruit, featured malaise, nausea and vomiting, followed by repeated convulsions and died even though undergoing conventional hemodialysis therapy.

Trasplante renal aislado o doble trasplante riñón-páncreas en pacientes con diabetes: indicaciones, ventajas y posibles complicaciones

Diabetic nephropathy is one of the main causes of renal failure and inclusion in a dialysis and transplant program. Kidney allograft can be made from a living or cadaver donor. Using living kidney transplant permits an early or preventive transplantation as compared to cadaver kidney allograft transplantation, which can be performed either as a single organ or combined with a pancreas transplantation. The choice of any kind of transplantation modality depends on age, type of diabetes and state of chronic diabetic complications. Each transplant modality has its advantages and disadvantages. Single kidney allograft is technically easier and less immunogenic, but it not allows complete metabolic control that can be achieved with simultaneous pancreas transplantation. The early complications are more frequent with kidney-pancreas transplant. But in the long-term, carbohydrate metabolism normalization achieved by the functioning pancreas allograft avoids recurrence of nephropathy in the kidney allograft, improves neuropathy and decreases cardiovascular mortality.

Bortezomib-Doxorubicin-Dexamethasone (BDD) in Patients with Acute Light Chain Induced Renal Failure (ARF) in Multiple Myeloma (MM). Final Results of a Phase II Study.

Abstract 3862Poster Board III-798Acute light chain (LC) induced renal failure (ARF) is a severe complication of progressive MM. Reversal of ARF can only be achieved by fast, substantial and continuous suppression of production of pathogenic LCs. Bortezomib is highly effective and well tolerated in myeloma patients (pts) with renal impairment, because its metabolism is independent of renal function. In this study we evaluated the efficacy of Bortezomib in combination with doxorubicin and dexamethasone (BDD) in restoring renal function and in achieving tumor control in pts with LC-induced renal failure. In total, 72 pts have been enrolled; 2 pts did not fulfil inclusion criteria, 2 pts had been excluded because kidney biopsy revealed renal amyloidosis as main cause of renal failure. Hence, 68 pts constituted the intent to treat population and 58 pts were evaluable per protocol (≥2 cycles of therapy). Age: median 65.8; range 41-79 years. Forty-six (79%) pts presented with de novo MM, and 12 (21%) with progressive, previously treated disease; median baseline GFR was 20.0 ml/min (range 3.7-49.5 ml/min). ARF was defined as decrease in GFR to <50ml/min due to LC nephropathy. Previously treated pts were required to have acute deterioration (< 4 weeks before inclusion) of formerly normal renal function (GFR „d60ml/min), and clear signs of progressive disease with increased LC excretion. Treatment regimen: Bortezomib (1.3mg/m2, d 1, 4, 8, 11 until the first safety analysis; thereafter 1.0mg/m2, d 1, 4, 8, 11), doxorubicin (9mg/m2, d 1, 4, 8, 11 until first safety analysis; thereafter 9mg/m2, d 1 and 4) and dexamethasone 40mg (d 1, 4, 8, 11). Cycles were repeated every 21 days. Renal response was defined as complete (CRrenal, with GFR ≥60 ml/min), partial (PRrenal with GFR increase >100%, from <15 ml/min to 30-<60 ml/min), or minor (MRrenal with GFR increase >50%, either from <15 ml/min to 15-<30 ml/min or from 15-<30 ml/min to 30-<60 ml/min). Twenty-six of 58 evaluable pts achieved CR/nCR (45%), 10 (17%) VGPR, 9 (16%) PR and 4 (7%) MR (CR-MR: 85%). Median time to best tumor response was 88 days. Twenty-one (36%) pts achieved CRrenal, and 19 (33%) pts PR/MRrenal, respectively, yielding an ORRrenal of 69%. Three of the 9 dialysis dependent pts became dialysis independent. Median GFR increased from 20.0 ml/min (range: 3.7 – 50.2 ml/min) to 48.4 ml/min (range 6.7 – 135.5 ml/min). Improvement of GFR correlated weakly with tumor response. The median of best GFR increased to 60.0 ml/min (14.7-131.3 ml/min) in the 36 pts with CR/nCR/VGPR, to 38.9 ml/min (14.7 – 135.5 ml/min) in the 13 pts with PR/MR, and to 16.8 ml/min (6.7 – 57.9 ml/min) in 9 the pts with SD/PD, respectively. Overall survival (OS) was 72% @ 1 and 60% @ 2 years in the intent to treat and 84% @ 1 and 70% @ 2 years in the evaluable population. OS was similar in pts with and without complete renal response (p= 0.9267). Univariate analysis revealed a significant association between both, treatment status (previously treated vs. not previously treated), and LDH with survival (p<0.0003, and p<0.0232, respectively), while in multivariate analysis (Cox regression) treatment status only was found to correlate with survival (p=0.0211). Leukopenia, thrombopenia, and anemia of grade 3&4 were seen in 12%, 14% and 48%, respectively. Other common grade 3&4 toxicities were weakness/fatigue (12%) and polyneuropathy (10%), infection (7%), herpes reactivation (7%) and nausea/vomiting (5%). In conclusion, the BDD regimen resulted in high tumor (CR/nCR/VGPR: 62%, ORR: 85%) and renal response rates (CRrenal 36%, ORRrenal 69%). Improvement of renal function was more often seen in pts with significant tumor response and CRrenal was more likely in pts with less severe renal impairment. Treatment was well tolerated after dose adjustment. Disclosures:Ludwig:Celgene: Honoraria; Mundipharma: Honoraria; AMGEN: Honoraria; Ortho-Biotech : Honoraria; Janssen-Cilag: Research Funding; Roche: Honoraria. Hajek:Janssen-Cilag: Honoraria.