Renal Failure In Adults Research Articles

Ferric Citrate for the Prevention of Renal Failure in Adults with Advanced CKD: The FRONTIER Trial

Ferric Citrate for the Prevention of Renal Failure in Adults with Advanced CKD: The FRONTIER Trial

Mildronate ameliorates kidney injury and reduces inflammation in Sickle Cell Disease mice

INTRODUCTION: Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and chronic inflammation that affects multiple organs including kidney, liver, brain, spleen, and heart. Renal disease, the most common complication in SCD, is a progressive disease that begins in childhood as glomerular hyperfiltration, then advances to albuminuria, following by a fast decline in glomerular filtration. It may further progress to a renal failure in adults. More than 50% of SCD patients develop chronic kidney disease (CKD), and 14-18% progress to the end-stage kidney disease. Renal injury in SCD results from a cascade of events starting with chronic red blood cells sickling and hemolysis leading to increased blood viscosity, microvascular obstruction and dilation, hypoxia in the medulla, oxidative stress, and inflammation. Mildronate (meldonium) is an anti-ischemic and anti-inflammatory medication approved in Eastern Europe. HYPOTHESIS: We hypothesized that mildronate administration reduces renal medullary hypoxia and decreases oxidative stress and inflammation ameliorating renal injury in SCD mice. METHODS: The study was approved by the Howard University IACUC. Townes SCD mice, expressing human HbS, and control mice, expressing human HbA, were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood was collected and used for hematological parameters analysis. Cytokines were measured by Bio-Plex suspension array in plasma. Hypoxyprobe Biotin kit (Hypoxyprobe Inc) was used for visualization of organ hypoxia. The effect of Mildronate on systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). Urinary KIM-1 was measured by TIM-1/KIM-1 ELISA kit (R&D Systems). RESULTS: Mildornate injections did not affect hematological parameters of SCD mice including hematocrit, MCV, MCH, CMCH, erythrocytes and hemoglobin. Mildronate administration resulted in a significant reduction of the circulating pro-inflammatory cytokines IFN-γ, IL-1β and TNF-α and a trend toward reduction of IL-6, and IL-17 in SCD mice. We found higher level of hypoxia in the medulla of SCD mice compared to control mice. Mildronate injections did not reduced hypoxia in renal medulla of SCD mice. Also, mildronate injections did not change MDA levels in plasma or kidney of SCD mice. We found a significant reduction of proteinuria in SCD mice injected with mildronate compared to SCD mice injected with vehicle. Analysis of H&E-stained kidneys showed significant reduction of glomerular size and medullar congestion areas in the mildronate injected SCD mice. Urinary KIM-1 levels were reduced by mildronate administration. CONCLUSIONS: Our results demonstrate that mildronate ameliorates glomerular and tubular injury in SCD mice and reduces capillary congestion. Mildronate improves renal function, in part by reducing inflammation but not through the reduction of hypoxia or oxidative stress. In future, we plan to assess the mildronate’s impact on kidney function and vessel inflammation. This work was supported by NIH grants R01HL125005, U54MD007597, and SC1HL150685. We thank Xiaomei Niu for helping with the Bio-Plex assay. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice.

Heterozygous DNAJB11 mutation carriers manifest with small cystic kidneys and renal failure in adulthood. Recessive cases with prenatal cystic kidney dysplasia were recently described. Our in vitro and mouse model studies investigate the proposed disease mechanism as an overlap of autosomal-dominant polycystic kidney disease and autosomal-dominant tubulointerstitial kidney disease pathogenesis. We find that DNAJB11 loss impairs cleavage and maturation of the autosomal-dominant polycystic kidney disease protein polycystin-1 (PC1) and results in dosage-dependent cyst formation in mice. We find that Dnajb11 loss does not activate the unfolded protein response, drawing a fundamental contrast with the pathogenesis of autosomal-dominant tubulointerstitial kidney disease. We instead propose that fibrosis in DNAJB11 -kidney disease may represent an exaggerated response to polycystin-dependent cysts. Patients with heterozygous inactivating mutations in DNAJB11 manifest with cystic but not enlarged kidneys and renal failure in adulthood. Pathogenesis is proposed to resemble an overlap of autosomal-dominant polycystic kidney disease (ADPKD) and autosomal-dominant tubulointerstitial kidney disease (ADTKD), but this phenotype has never been modeled in vivo . DNAJB11 encodes an Hsp40 cochaperone in the endoplasmic reticulum: the site of maturation of the ADPKD polycystin-1 (PC1) protein and of unfolded protein response (UPR) activation in ADTKD. We hypothesized that investigation of DNAJB11 would shed light on mechanisms for both diseases. We used germline and conditional alleles to model Dnajb11 -kidney disease in mice. In complementary experiments, we generated two novel Dnajb11-/- cell lines that allow assessment of PC1 C-terminal fragment and its ratio to the immature full-length protein. Dnajb11 loss results in a profound defect in PC1 cleavage but with no effect on other cystoproteins assayed. Dnajb11-/- mice are live-born at below the expected Mendelian ratio and die at a weaning age with cystic kidneys. Conditional loss of Dnajb11 in renal tubular epithelium results in PC1 dosage-dependent kidney cysts, thus defining a shared mechanism with ADPKD. Dnajb11 mouse models show no evidence of UPR activation or cyst-independent fibrosis, which is a fundamental distinction from typical ADTKD pathogenesis. DNAJB11 -kidney disease is on the spectrum of ADPKD phenotypes with a PC1-dependent pathomechanism. The absence of UPR across multiple models suggests that alternative mechanisms, which may be cyst-dependent, explain the renal failure in the absence of kidney enlargement.

Favism: Clinical Features at Different Ages.

Favism is a hemolytic disease due to the ingestion of fava beans in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. There is wide inter- and intra-individual variability in the development of hemolytic crisis, and several factors influence it: quantity, quality, ripeness of fava beans, and age of onset. In this narrative review of case reports and case series, we reported the predisposing factors and clinical features for four different age groups classified as follows: pregnant women and infants (i.e., exclusively breastfed children); children, from weaned to 11 years; preadolescents and adolescents, from 11 to 18 years; and adults (18 years and older). Some symptoms developed only in specific age groups: death in infants; visual impairment in children; systolic murmur in infants, children, and adolescents; and renal failure in adults. In youngest children or pregnant women the severity is the highest. Some other symptoms were present in all: jaundice, increased bilirubin, splenomegaly, hepatomegaly, discolored urine, tachycardia, pallor, abdominal pain, malaise, vomit, nausea, and dizziness. Laboratory findings are characterized by anemia, reticulocytosis, elevated bilirubin level, and sometimes urinary urobilinogen and methemoglobinemia. In most cases the symptomatology is self-limited and does not release sequelae, but hospitalization and transfusion are often required.

Glomerular filtration rate abnormalities in sickle cell disease.

Sickle cell disease (SCD) is a group of inherited blood disorders affecting the β-globin gene, resulting in the polymerization of hemoglobin and subsequent sickling of the red blood cell. Renal disease, the most common complication in SCD, begins in childhood with glomerular hyperfiltration and then progresses into albuminuria, a fast decline of glomerular filtration, and renal failure in adults. This mini-review focuses on glomerular filtration abnormalities and the mechanisms of hyperfiltration, explores genetic modifiers and methods of estimating glomerular filtration rates, and examines novel biomarkers of glomerular filtration in SCD.

Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids

Persistent Aseptic Pyelonephritis After Acute Bacterial Pyelonephritis: Possible Role of Corticosteroids

Https://theijmed.com/index.php?journal=theijmed&page=issue&op=view&path%5B%5D=24

Background: Heavy metals, such as cadmium, are heavy metals that are hazardous to health. Chronic exposure to cadmium is associated with decreased glomerular filtration rate and increased risk of chronic renal failure. This study was conducted to determine how much influence cadmium exposure has on the incidence of chronic kidney failure in adults. The purpose of this study was to analyze the effect of cadmium exposure on the incidence of chronic kidney failure in adults. Subject and Method : This study is a systematic review and meta-analysis using the PRISMA flowchart with PICO as follows, Population: Adults. Intervention: Exposure to Cadmium. Compa­rison: No Cadmium Exposure. Outcome: Chronic Renal Failure. Search articles using several data­bases including PubMed, Google Scholar, and Science Direct with the search keywords “adults” AND “cadmium exposure” AND “chronic kidney failure”. The articles submitted ranged from 2013 to 2021. Analysis was performed using RevMan 5.3 as a statistical program. Results : There are 11 articles, originating from the continents of Asia and Europe. The results of the meta-analysis showed that exposure to cadmium increased the risk of developing chronic renal failure in adults by 2.81 times compared with adults who were not exposed to cadmium and was statistically significant (aOR = 2.81; 95% CI = 1.74 to 4.51; p < 0.001). Conclusion: Cadmium exposure may increase the risk of chronic kidney failure in adults. Keywords: cadmium, chronic renal failure, adults Correspondence: Fathia Mutiara Zahra. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: efemzahra31@student.uns.ac.id. Mobile: +62 815-6798-7661. Indonesian Journal of Medicine (2022), 07(01): 61-72 https://doi.org/10.26911/theijmed.2022.07.01.07

Case Report on Chronic Renal Failure in Adults

Introduction: CRF is either the presence of kidney damage for 3 months or longer. Kidney damage is defined as either pathologic abnormalities or markers of damage including abnormalities in blood or urine test or imaging studies. Chronic disease are defined broadly as conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both. Chronic disease such as heart disease, cancer, and diabetes are the leading causes of death and disability in the individual. As renal function declines, the end products of protein metabolism (normally excreted in urine) accumulate in the blood. Uremia develops and adversely affects every system in the body the greater the buildup of waste products, the more pronounced the symptoms. The rate of decline in renal function and progression of end stage kidney disease is related to the underlying disorder.
 Main Symptoms of CRF: The main signs and symptoms-Fever/cough/cold/abdominal pain/vomiting/loose stool/edema/giddiness/back pain. Abnormal blood loss in urine test, high blood pressure, weight loss for no reason, low red blood cell count (anemia), nausea, metal taste in your mouth, loss of appetite.
 Diagnostic Evaluation: blood test: Hb-6.5gm%, total RBC count-3.5million/cu mm, HCT-28.4%, total WBC count-9.6/cu mm. monocytes-03%, granulocytes-85%, lymphocytes-10%,calcium-9.1mg/day, creatinine-urine test-71.8mg/dl, KFT- urea-111mg/dl, cretinine14.0, sodium 134mmol/l, potassium-6.5(pl. repeat), magnesium-2.4mmol/l, phosphorus-7.3mmol/l, RBS glucose-plasma random -222mmhg, uric acid -8.1mg/dl, urinary protein- 905mg/dl, bloodpressure-140/90mmhg.
 Therapeutic interventions: inj. Levoflox 500mg IV OD, inj. ctri 1gm IV BD X 5days, inj. Pan 40mg IV OD, inj. Emset 4mg IV OD, inj. Insulin m(30/70) 18u(BFF)-0-12u(BD) inj. EPO 10000 IU SC post dialysis once per week, tab. Nicardia 20mg TDS, tab. Febuxostat 40mg OD, tab. Shelcal 500mg OD, tab. autrin OD, tab. Sevelamer 400mg BD, tab. Envas 5mg HS, tab. met XL 25mg OD.
 Outcome: after treatment, the adult show improvement. His abdominal pain were relieved and his diabetes and hypertension were in control.
 Causes: Due to some disease of infection the kidney can’t do its works properly, the main cause of chronic renal failure is High blood pressure Blocked urinary tract. The chief causes of CRF include obstructive uropathy, primary glomerular diseases, reflux nephropathy and hypoplastic or dysplastic kidneys. Progressive hyperperfusion and hyerfilteration causes increasing glomerular injury and further renal damage. Symptoms of CRF is between 10-25% of normal. The four main causes of CRF are high blood pressure, chronic glomerulonephritis, high blood sugar, polycystic kidney disease.
 Conclusion: My patient was a known case of chronic renal failure and he had complaint of irritation abdominal pain, back pain, giddiness. After getting proper treatment his condition was better than previous condition.

Trial Design of FRONTIER: Ferric Citrate for the Prevention of Renal Failure in Adults with Advanced CKD

Trial Design of FRONTIER: Ferric Citrate for the Prevention of Renal Failure in Adults with Advanced CKD

The impact of constant antibiotic prophylaxis in children affected by spinal dysraphism performing clean intermittent catheterization: a 2-year monocentric retrospective analysis

IntroductionSpinal dysraphism (SD) is a general term used to refer to developmental abnormalities of the spine that involves many clinical conditions including myelomeningocele (MMC). In these patients, neurogenic bladder (NB) is a common and predisposing factor for renal damage; the most frequently used approach to manage this situation is based on clean intermittent catheterization (CIC) and anticholinergic drugs. Urinary tract infections (UTIs) are a significant concern for these patients, and antibiotic prophylaxis is frequently used even if it is still a debated topic of literature. The purpose of this paper is to investigate the role and the real effectiveness of antibiotic prophylaxis in the reduction of incidence of UTIs in patients with spina bifida performing CIC.MethodsWe collected data of all patients performing CIC, who did their last follow-up visit in the period between January 2019 and January 2021, followed at the children multidisciplinary Spina Bifida Center of A. Gemelli Hospital in Rome. Data collected included age at referral, gender, type of SD lesion, serum creatinine and cystatin C levels, the use of anticholinergic medications, antibiotic prophylaxis and type of prophylaxis (oral/endovesical), age of starting prophylaxis with its duration/adherence, number of CIC/day and its duration, episodes of UTIs in the 2 years prior to the last follow-up, and presence and grade of vesical-ureteric reflux (VUR) on cystourethrogram.ResultsA total of 121 patients with SD performing CIC was included in the study; 66 (54%) presented ≥ 1 episode of UTIs in the last two years and 55 (46%) none. During the study period, 85 (70%) patients received antibiotic prophylaxis (ABP group) and 36 (30%) did not (NABP group): no statistically significative difference in terms of UTI development was observed between the two groups (p = 0.17). We also evaluated compliance to the therapy; 71 patients (59%) took antibiotic prophylaxis constantly (CABP group) and 50 (41%) did not do antibiotic prophylaxis constantly or did not do antibiotic prophylaxis at all (NCABP group): we observed a statistically significative difference in terms of UTIs with a 2.2 times higher risk of development at least one episode of UTIs in NCABP group.ConclusionIn conclusion, antibiotic prophylaxis performed constantly, without interruption, is associated with a lower risk of developing urinary tract infections and consequently to develop renal failure in adulthood.

Management of Obstructive Renal Failure in Adults at the Sylvanus Olympio University Hospital

Background: Obstructive nephropathies are a topical issue in urology and nephrology consultations, but no study has yet been conducted on the subject in our country. Objective: Describe the epidemiological, clinical, therapeutic and evolutionary profile of obstructive nephropathies at the Sylvanus Olympio University hospital of Togo. Method: It was a descriptive and cross-sectional study with a collection of retrospective data over a period of 08 years (2012-2019) which focused on obstructive nephropathies in the Urology-Andrology, Nephrology and Internal Medicine departments at the medical clinic of CHU SO. The diagnosis of obstructive nephropathy is retained on the basis of radiological and medical imaging results. Results: The study population included 131 patients. The annual hospital frequency was 2.84 cases for 100 admissions. The mean age was 56.72 ± 17.76 years. These patients were mostly male (72.52%). The most frequent age group was 60 - 80 years. Common symptoms at presentation were loin pain (45.75%) and dysuria (25.95%). The average length of probable course of the disease before hospitalization was 636.94 ± 258.88 days (21 months). The etiologies of obstructive nephropathy were largely dominated by prostatic tumors in half of the cases (45.80%). Among these patients, 121 have presented renal failure (92.36%). The average serum creatinine at admission was 59.01 ± 21.56 mg/l. Of the 121 patients with obstructive nephropathy presenting renal failure, 54 (44.63%) had decreased their serum creatinine at the output of more than 25%. The open surgery (54.20%) was the main treatment. There was an improvement in kidney function in patients who had a shorter duration of disease progression and who did not have a history of loin pain, oliguria and that the etiologies of the disease were not tumors. Tumoral etiologies, the presence of a history of high blood pressure, oedema of the lower members, oliguria, and a longer duration of disease progression and sex were factors associated with the occurrence of end-stage renal disease. Conclusion: Renal failure is the main complication of obstructive nephropathy in Togo, hence the importance of an early diagnosis for better care.

A Multitubular Kidney-on-Chip to Decipher Pathophysiological Mechanisms in Renal Cystic Diseases.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major renal pathology provoked by the deletion of PKD1 or PKD2 genes leading to local renal tubule dilation followed by the formation of numerous cysts, ending up with renal failure in adulthood. In vivo, renal tubules are tightly packed, so that dilating tubules and expanding cysts may have mechanical influence on adjacent tubules. To decipher the role of this coupling between adjacent tubules, we developed a kidney-on-chip reproducing parallel networks of tightly packed tubes. This original microdevice is composed of cylindrical hollow tubes of physiological dimensions, parallel and closely packed with 100–200 μm spacing, embedded in a collagen I matrix. These multitubular systems were properly colonized by different types of renal cells with long-term survival, up to 2 months. While no significant tube dilation over time was observed with Madin-Darby Canine Kidney (MDCK) cells, wild-type mouse proximal tubule (PCT) cells, or with PCT Pkd1+/- cells (with only one functional Pkd1 allele), we observed a typical 1.5-fold increase in tube diameter with isogenic PCT Pkd1-/- cells, an ADPKD cellular model. This tube dilation was associated with an increased cell proliferation, as well as a decrease in F-actin stress fibers density along the tube axis. With this kidney-on-chip model, we also observed that for larger tube spacing, PCT Pkd1-/- tube deformations were not spatially correlated with adjacent tubes whereas for shorter spacing, tube deformations were increased between adjacent tubes. Our device reveals the interplay between tightly packed renal tubes, constituting a pioneering tool well-adapted to further study kidney pathophysiology.

POS-137 PREDICTIVE FACTORS OF CHRONIC KIDNEY FAILURE IN POST-INFECTIOUS ACUTE GLOMERULONEPHRITIS IN ADULTS

Post-infectious acute glomerulonephritis (post-infectious GNA) is an acute glomerulonephritis resulting from an immunological reaction secondary to an infection. It presents clinically as an acute nephritic syndrome with macroscopic or microscopic haematuria, proteinuria, oedematous syndrome, arterial hypertension and renal failure. Post-infectious GNA is frequent in children with favourable evolution, but in adults the evolution is uncommon. We conducted a retrospective descriptive and analytic study; on data from 54 patients diagnosed with post-infectious GNA between 1980 and 2020. The median age was 37.5 years (minimum=15 years, maximum=65 years), the sex ratio was 4.4. The percentage of patients with a history of diabetes was 7,4%, hypertension 7,4%, history of recurrent angina 10%. Infection was noted in 31 of the patients with the most frequent site observed to be upper respiratory tract. The median creatinine and proteinuria of 24 hour on admission was 150 mmol and 2.6 g/24h respectively. All patients have benefited renal puncture biopsy which showed endocapillary and extracapillary proliferation in 22.5% of cases. The percentage of patients who presented a persistence of urinary sediment abnormalities during surveillance was 62.5% for hematuria and proteinuria at the urinary strip. It was noted that 25.9% of patients presented a persistence of proteinuria of 24 hours. The end-stage renal failure was noted in 7.5% of patients. In univariate analysis; the persistence of 24h proteinuria was a significant predictive factor of chronic renal failure (p=0.01). The most predictive factor for chronic renal failure in adults diagnosed with post-infectious GNA is the persistence of 24-hour proteinuria.

ESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease

Acute kidney disease (AKD) - which includes acute kidney injury (AKI) - and chronic kidney disease (CKD) are highly prevalent among hospitalized patients, including those in nephrology and medicine wards, surgical wards, and intensive care units (ICU), and they have important metabolic and nutritional consequences. Moreover, in case kidney replacement therapy (KRT) is started, whatever is the modality used, the possible impact on nutritional profiles, substrate balance, and nutritional treatment processes cannot be neglected. The present guideline is aimed at providing evidence-based recommendations for clinical nutrition in hospitalized patients with AKD and CKD. Due to the significant heterogeneity of this patient population as well as the paucity of high-quality evidence data, the present guideline is to be intended as a basic framework of both evidence and - in most cases - expert opinions, aggregated in a structured consensus process, in order to update the two previous ESPEN Guidelines on Enteral (2006) and Parenteral (2009) Nutrition in Adult Renal Failure. Nutritional care for patients with stable CKD (i.e., controlled protein content diets/low protein diets with or without amino acid/ketoanalogue integration in outpatients up to CKD stages four and five), nutrition in kidney transplantation, and pediatric kidney disease will not be addressed in the present guideline.

Polycystic kidney disease and other genetic kidney disorders

Cystic kidney diseases encompass a range of genetic disorders in which the primary cilia of the cells are affected and thereby cysts form as a result. There are an increasing range of cystic renal diseases recognized due to the advances in genomics. The most common genetic kidney condition is autosomal dominant polycystic kidney disease (ADPKD). ADPKD leads to renal failure in adulthood. In children, hypertension is common and if treated, may slow down renal decline. The most common cystic kidney disease causing renal failure in children is autosomal recessive polycystic kidney disease (ARPKD). ARPKD also affects the liver. These conditions often have extra-renal features which also need to be addressed. Until recently, treatments were mainly supportive but now it is possible to slow down development of cyst formation and renal decline in ADPKD. This raises hope for treatment for other cystic renal conditions as more genes are identified and underlying mechanisms defined.

P0334HEMOLYTIC UREMIC SYNDROME: CLINICAL PRESENTATION, LABORATORY FINDINGS, MANAGEMENT AND OUTCOMES

Abstract Background and Aims Hemolytic-uremic syndrome (HUS) is a disease that has been described as a triad of hemolytic anemia, thrombocytopenia and renal impairment. There are two types of HUS, typical and atypical. HUS remains a leading cause of acute renal injury in children and is increasingly recognized as a cause of renal failure in adults. In our study we evaluated the demographic features, clinical characteristics, management and outcome of HUS. Method This is a descriptive study evaluating all cases of Hemolytic Uremic Syndrome (HUS) that have been admitted at Royal Hospital (RH) Oman in the period between 2008 and 2017. Results Thirty-six patients identified. The mean age (SD) of 10.68 (14.07) years. Eighteen (50%) presented with abdominal pain, nausea, vomiting and diarrhea, 9 (25 %) with hypertension, 23 (64 %) with acute kidney injury (AKI), 6 (16.67%) with seizure, 2 (5.56%) with confusion and 1 (2.78%) with cerebrovascular accident (CVA). Twenty-one (58.33 %) diagnosed as typical HUS of which 19 with Shiga toxin producing Escherichia Coli (STEC) HUS and 2 had post Streptococal HUS. Six (16.67%) diagnosed with aHUS, 2 (5.56%) with HELLP, 2 (5.56%) with G6PD, 3 (8.33%) with Autoimmune hemolytic anemia (AIHA ), one (2.78%) with congenital TTP and 1 (2.78%) with post partum HUS. Twenty three (63.89%) needed renal replacement therapy (RRT), while remaining 13 (36.11%) did not require RRT. Eleven (30.56%) received plasma exchange, 5 (13.89%) received Eculizumab while 2 (5.56%) received plasma infusion and 1 (2.78%) patient received Rituximab. The majority 22 (61.11%) had partial recovery after treatment, 5 (13.89 %) had compelte recovery and 3 (8.33% ) ended with end stage kidney disease (ESKD) and 1 (2.78%) died from hypertensive crises. Conclusion The study results showed that HUS population were mostly due to Shiga toxin producing Escherichia Coli (STEC). It showed that HUS population were young, mostly male and only 25% have known medical comorbidities at time of presentation. Also, the majority presented with AKI requiring dialysis, of which PD was main stay of therapy. The duration of RRT and recovery time was almost a month period.

P0433AGE-RELATED DIFFERENCES IN THE SPECTRUM OF BIOPSY-PROVEN GLOMERULONEPHRITIS

Abstract Background and Aims The proportion of geriatric population is increasing globally and age-related changes, as kidney ageing and decline in immunocompetence, might interfere with frequency of various glomerulopathies (GP). Thus, it is conceivable that the spectrum of biopsy-proven GP varies across different age categories. Accordingly, we aimed to describe age-related variation in clinical presentation and the in prevalence of GP diagnosed by kidney biopsy (KB) in adults. Method This retrospective study enrolled 1254 subjects selected from the KB database of a large tertiary academic Nephrology center (which provides specialized care for the south-eastern part of our country), over a ten-year span (01.01.2008-31.12.2017). Inclusion criteria were age >18 years, native kidney biopsy, availability of data from light, immunofluorescence, and electron microscopy, and a histologic diagnosis of GP. Repeated biopsies and inadequate tissue samples were excluded. Demographic (age, gender), clinical and laboratory data at the time of biopsy were extracted from medical records for all the selected subjects. To investigate the possible influence of age on the spectrum of biopsy-proven GP, the cohort was divided into 4 categories: young adults (18 to 30 years, n=156), adults (31 to 64 years, n=868), elderly (65 to 74 years, n=176) and very elderly (≥75 years, n=54), and the collected data were compared by non-parametric methods (Mann-Whitney, Chi2 and Fisher exact tests). Results The nephrotic syndrome was the most common presentation form in all age groups but had a higher prevalence in very elderly (62%) and elderly (55%) as compared to adults (37%, p=0.01) and young adults (41%, p<0.001). In the groups below age of 65, the chronic nephritic syndrome was the second most common indication for KB (31% and 28%, respectively), followed by chronic renal failure in adults (13%) and acute nephritic syndrome in young adults (10%). Lupus nephritis (LN) and IgA nephropathy (IgAN) were the most commonly diagnosed GP in young adults (22% each), followed by minimal change disease (MCD, 14%), membranous nephropathy (MN, 8%), focal and segmental glomerulosclerosis (FSGS, 8%), and thin basement membrane disease (6%). In adults, the most common GP were: IgAN (23%), MN (15%), diabetic nephropathy (DN, 11%) and MCD (10 %). Conversely, in both the elderly and the very elderly, the most common biopsy-proven GP was MN (26% each). Elderly had renal amyloidosis as the second most prevalent histological diagnosis (17%), followed by DN (11%), and by IgAN and MCD (≈10% each). Crescentic glomerulonephritis (CGN) occurred in 7.5% of the elderly, but it was the second pathology (17%) in subjects aged 75+ years, followed by MCD (15%) and DN (13%). IgAN and amyloidosis were identified in about 5% of this group. It appears that the prevalence of both clinical presentation and histologically diagnosed GP showed some similarities between the first two and, respectively, last two age categories. Conclusion Biopsy-proven GP have different frequencies depending on the patient’s age, with some pathologies predominantly found at older ages (such as membranous nephropathy, amyloidosis and crescentic GN) or, on the contrary, typical for young adults (lupus nephritis and IgAN). These differences account for the distinct clinical presentations at the time of KB.

Essential Residues Required for the Opening of a Polycystin TRP Channel

Polycystins (PKD2 and homologs) belong in the family of the Transient Receptor Potential (TRP) nonselective cation channels. Their biophysics and cellular functions are still poorly understood, except for their association with autosomal dominant polycystic kidney disease (ADPKD), a common monogenetic disorder characterized by proliferative cysts which leads to renal failure in adulthood. TRP channels are known to be stimulated by a wide range of external stimuli, where some classes are thermo-sensitive, ligand-gated, while others are regulated by osmotic stress or extracellular pH. Despite the diversity, TRP channels are not traditionally considered as voltage-gated, or being activated in response to changes in the membrane potential. Here, we examined the property of PKD2-L1 (also called TRPP3)- a member of the polycystin sub-class of TRP channels. Endogenously, PKD2-L1 forms heteromeric channels with other polycystins in the primary cilia, but can also form a homomeric channel when expressed heterologously. We investigated on the structural movements which control voltage-dependent and polymodal gating of the homomeric form of this channel. Through analysis of new functional and structural data sets, we have defined a series of interactions which are absolutely essential for channel opening.

Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions.

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic inherited renal cystic disease that occurs in different races worldwide. It is characterized by the development of a multitude of renal cysts, which leads to massive enlargement of the kidney and often to renal failure in adulthood. ADPKD is caused by a mutation in PKD1 or PKD2 genes encoding the proteins polycystin-1 and polycystin-2, respectively. Recent studies showed that cyst formation and growth result from deregulation of multiple cellular pathways like proliferation, apoptosis, metabolic processes, cell polarity, and immune defense. In ADPKD, intracellular cyclic adenosine monophosphate (cAMP) promotes cyst enlargement by stimulating cell proliferation and transepithelial fluid secretion. Several interventions affecting many of these defective signaling pathways have been effective in animal models and some are currently being tested in clinical trials. Moreover, the stem cell therapy can improve nephropathies and according to studies were done in this field, can be considered as a hopeful therapeutic approach in future for PKD. This study provides an in-depth review of the relevant molecular pathways associated with the pathogenesis of ADPKD and their implications in development of potential therapeutic strategies.

S34. A novel case of axonal form of adult Guillain Barré Syndrome (GBS) preceded by acute renal failure

Guillain Barré syndrome is an acute/subacute form of polyradiculoneuropathy that can cause, commonly, ascending paraplegia and sensory deficits, and can result in quadriplegia, respiratory failure requiring intubation. There are different subtypes of GBS – e.g. motor, motor-sensory, Miller Fisher syndrome and others. Axonal form of GBS is the predominant form in the pediatric population in the US and many Asian countries. There is paucity of literature about such cases preceded by acute renal failure in adults. Reporting a patient admitted to Neurology inpatient service in a tertiary care center in Central Pennsylvania. A PubMed search was done. 72 year-old man presented with acute onset of paraplegia and areflexia shortly after acute renal failure- confirmed by laboratory testing, and was intubated for respiratory failure. Besides respiratory compromise, there was no cranial nerve or autonomic involvement. Sensory impairment was restricted to the lower extremities only. Infectious workup was unrevealing. CSF studies showed albuminocytologic dissociation. MRI of brain and entire spine did not show any significant abnormalities. EMG showed severe, generalized, axonal, motor and sensory polyneuropathy. GBS was diagnosed based on clinical features supported by CSF. Patient received a course of IVIG without improvement. Plasmapheresis was subsequently done. He was successfully extubated without any improvement of his motor and sensory profile. Acute axonal form of GBS causing diffuse motor and sensory neuropathy usually has an early age of onset, slower recovery and incomplete resolution of symptoms. This is a novel case of axonal variant of GBS preceded by renal failure, as per our review of literature for North America. A broad differential diagnoses should be kept in mind in patients with acute/subacute paraplegia preceded by acute renal failure.