Severe Kidney Disease Research Articles

A segmentation procedure of the pervious area of the aorta artery from CT images without contrast medium

In this paper, we develop an algorithm for the segmentation of the pervious lumen of the aorta artery in computed tomography (CT) images without contrast medium, a challenging task due to the closeness gray levels of the different zones to segment. The novel approach of the proposed procedure mainly resides in enhancing the resolution of the image by the application of the algorithm deduced from the mathematical theory of sampling Kantorovich operators. After the application of suitable digital image processing techniques, the pervious zone of the artery can be distinguished from the occluded one. Numerical tests have been performed using 233 CT images, and suitable numerical errors have been computed and introduced ex novo to evaluate the performance of the proposed method. The above procedure is completely automatic in all its parts after the initial region of interest (ROI) selection. The main advantages of this approach relies in the potential possibility of performing diagnosis concerning vascular pathologies even for patients with severe kidney diseases or allergic problems, for which CT images with contrast medium cannot be achieved.

Differential methylation pattern of xenobiotic metabolizing genes and susceptibility to Balkan endemic nephropathy, in a cohort of Romanian patients.

A severe, chronic and irreversible kidney disease affecting discrete rural populations in the Balkan Peninsula countries, Balkan endemic nephropathy (BEN) has been a scientific puzzle for more than half a century. Many environmental and other factors have been suggested as the primary cause and recent significant findings have linked BEN to aristolochic acids, phytotoxins derived from the plant Aristolochia clematitis, found in high density in the endemic areas. However, given that the incidence of BEN is less than 10% in affected villages, and it tends to have a family aggregation, as yet unidentified genetic factors may also play a role. To further explore this possibility, a pilot study was initiated to investigate the DNA methylation of CYP1A1, CYP1A2, NAT1, NQO1 and GSTT1 in blood samples from a group of Romanian BEN patients, compared to healthy controls and non-BEN chronic kidney disease (CKD) subjects. Our study revealed a more pronounced hypomethylation pattern in BEN and non-BEN CKD groups, compared to the healthy control group at specific CpGs across all five genes interrogated. Average methylation across the five regions investigated indicated significant differences only at GSTT1, in both BEN patients (p = 0.028) and non-BEN disease subjects (p = 0.015), relative to healthy individuals. Since GSTT1 active genotype appears to be a common feature of Serbian and Romanian BEN patients, GSTT1 epigenetic variation and increased gene activity could act as a predisposing (co)factor in BEN populations from the affected countries. BEN and non-BEN CKD groups show similar methylation patterns with exception of GSTT1 CpG8 (p = 0.046).

Association of Undifferentiated Dyspnea in Late Life With Cardiovascular and Noncardiovascular Dysfunction

Undifferentiated dyspnea is common in late life, but the relative contribution of subclinical cardiac dysfunction is unknown. Impairments in cardiac structure and function may be characteristics of undifferentiated dyspnea in elderly people, providing potential insights into occult heart failure (HF). To quantify the association of undifferentiated dyspnea with cardiac dysfunction after accounting for other potential contributors. This cross-sectional study used data from Atherosclerosis Risk in Communities study participants 65 years and older who attended the fifth study visit (from 2011 to 2013) and had not been diagnosed with HF, chronic obstructive pulmonary disease, morbid obesity, or severe kidney disease. Analyses were conducted from October 2017 to June 2018. Dyspnea measured using the modified Medical Research Council scale, with a score less than 2 classified as none to mild and a score of 2 or more classified as moderate to severe. Using multivariable logistic regression, the association of undifferentiated dyspnea was defined using cardiac structure, systolic and diastolic function, pulmonary pressure (echocardiography), pulmonary function (spirometry), glomerular filtration rate, hemoglobin, body mass index, depression, and physical performance. The population-attributable risk was calculated for each dysfunction metric. Among 4342 participants (mean [SD] age, 75.9 [5.0] years; 2533 [58.3%] women), 1173 (27.0%) had undifferentiated dyspnea. Moderate to severe dyspnea was present in 574 participants (13.2%) and was associated with left ventricular (LV) hypertrophy (odds ratio [OR], 1.53; 95% CI, 1.25-1.87; P < .001) and LV diastolic (OR, 1.46; 95% CI, 1.20-1.78; P < .001) and systolic (OR, 1.28; 95% CI, 1.05-1.56; P = .02) dysfunction. Moderate to severe dyspnea was also associated with obstructive (OR, 1.59; 95% CI, 1.28-1.99; P < .001) and restrictive (OR, 2.56; 95% CI, 1.99-3.27; P < .001) findings on spirometry, renal impairment (OR, 1.32; 95% CI, 1.08-1.61; P = .01), anemia (OR, 1.72; 95% CI, 1.39-2.12; P < .001), lower (OR, 2.77; 95% CI, 2.18-3.51; P < .001) and upper (OR, 1.82; 95% CI, 1.49-2.23; P < .001) extremity weakness, depression (OR, 3.01; 95% CI, 2.24-4.25; P < .001), and obesity (OR, 2.35; 95% CI, 1.95-2.83; P < .001). After accounting for these, moderate to severe dyspnea was associated with LV hypertrophy (OR, 1.30; 95% CI, 1.01-1.67; P = .04) and was not associated with systolic or diastolic function. In contrast, in the fully adjusted model, other organ system measures were associated with dyspnea, except for glomerular filtration rate and grip strength. The population-attributable risk of dyspnea associated with obesity alone was 22.6% compared with 5.8% for LV hypertrophy. Undifferentiated dyspnea is multifactorial in older adults, and this study showed an association with obesity. When accounting for other relevant organ systems, cardiovascular function poorly discriminated those with vs those without dyspnea. Therefore, dyspnea should not be assumed to represent occult HF in this population.

Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia.

To assess the impact of autologous cell therapy on critical limb ischaemia in people with diabetes and diabetic kidney disease. A total of 59 people with diabetes (type 1 or type 2) and critical limb ischaemia, persisting after standard revascularization, were treated with cell therapy in our foot clinic over 7 years; this group comprised 17 people with and 42 without severe diabetic kidney disease. The control group had the same inclusion criteria, but was treated conservatively and comprised 21 people with and 23 without severe diabetic kidney disease. Severe diabetic kidney disease was defined as chronic kidney disease stages 4-5 (GFR <30 ml/min/1.73 m²). Death and amputation-free survival were assessed during the 18-month follow-up; changes in transcutaneous oxygen pressure were evaluated at 6 and 12 months after cell therapy. Transcutaneous oxygen pressure increased significantly in both groups receiving cell therapy compared to baseline (both P<0.01); no significant change in either of the control groups was observed. The cell therapy severe diabetic kidney disease group had a significantly longer amputation-free survival time compared to the severe diabetic kidney disease control group (hazard ratio 0.36, 95% CI 0.14-0.91; P=0.042); there was no difference in the non-severe diabetic kidney disease groups. The severe diabetic kidney disease control group had a tendency to have higher mortality (hazard ratio 2.82, 95% CI 0.81-9.80; P=0.062) than the non-severe diabetic kidney disease control group, but there was no difference between the severe diabetic kidney disease and non-severe diabetic kidney disease cell therapy groups. The present study shows that autologous cell therapy in people with severe diabetic kidney disease significantly improved critical limb ischaemia and lengthened amputation-free survival in comparison with conservative treatment; however, the treatment did not influence overall survival.

Novel Orthobunyavirus Causing Severe Kidney Disease in Broiler Chickens, Malaysia, 2014-2017.

During 2014–2017, we isolated a novel orthobunyavirus from broiler chickens with severe kidney lesions in the state of Kedah, Malaysia; we named the virus Kedah fatal kidney syndrome virus (KFKSV). Affected chickens became listless and diarrheic before dying suddenly. Necropsies detected pale and swollen kidneys with signs of gout, enlarged and fragile livers, and pale hearts. Experimental infection of broiler chickens with KFKSV reproduced the disease and pathologic conditions observed in the field, fulfilling the Koch’s postulates. Gene sequencing indicated high nucleotide identities between KFKSV isolates (99%) and moderate nucleotide identities with the orthobunyavirus Umbre virus in the large (78%), medium (77%), and small (86%) genomic segments. KFKSV may be pathogenic for other host species, including humans.

C3-Glomerulopathy Autoantibodies Mediate Distinct Effects on Complement C3- and C5-Convertases

C3 glomerulopathy (C3G) is a severe kidney disease, which is caused by defective regulation of the alternative complement pathway. Disease pathogenesis is heterogeneous and is caused by both autoimmune and genetic factors. Here we characterized IgG autoantibodies derived from 33 patients with autoimmune C3 glomerulopathy. Serum antibodies from all 33 patients as well as purified IgGs bound to the in vitro assembled C3-convertase. Noteworthy, two groups of antibodies were identified: group 1 with strong (12 patients) and group 2 with weak binding C3-convertase autoantibodies (22 patients). C3Nef, as evaluated in a standard C3Nef assay, was identified in serum from 19 patients, which included patients from group 1 as well as group 2. The C3-convertase binding profile was independent of C3Nef. Group 1 antibodies, but not the group 2 antibodies stabilized the C3-convertase, and protected the enzyme from dissociation by Factor H. Also, only group 1 antibodies induced C3a release. However, both group 1 and group 2 autoantibodies bound to the C5-convertase and induced C5a generation, which was inhibited by monoclonal anti-C5 antibody Eculizumab in vitro. In summary, group 1 antibodies are composed of C3Nef and C5Nef antibodies and likely over-activate the complement system, as seen in hemolytic assays. Group 2 antibodies show predominantly C5Nef like activities and stabilize the C5 but not the C3-convertase. Altogether, these different profiles not only reveal a heterogeneity of the autoimmune forms of C3G (MPGN), they also show that in diagnosis of C3G not all autoimmune forms are identified and thus more vigorous autoantibody testing should be performed.

Retraction: Novel Orthobunyavirus Causing Severe Kidney Disease in Broiler Chickens, Malaysia, 2014-2017.

During 2014-2017, we isolated a novel orthobunyavirus from broiler chickens with severe kidney lesions in the state of Kedah, Malaysia; we named the virus Kedah fatal kidney syndrome virus (KFKSV). Affected chickens became listless and diarrheic before dying suddenly. Necropsies detected pale and swollen kidneys with signs of gout, enlarged and fragile livers, and pale hearts. Experimental infection of broiler chickens with KFKSV reproduced the disease and pathologic conditions observed in the field, fulfilling the Koch's postulates. Gene sequencing indicated high nucleotide identities between KFKSV isolates (99%) and moderate nucleotide identities with the orthobunyavirus Umbre virus in the large (78%), medium (77%), and small (86%) genomic segments. KFKSV may be pathogenic for other host species, including humans.

VII. Efforts for Prevention of Severe Diabetic Kidney Disease (DKD) in Community Medicine

VII. Efforts for Prevention of Severe Diabetic Kidney Disease (DKD) in Community Medicine

MON-617 The Determination of Peripheral Blood Apoptosis Factors and Its Clinical Significance in Hashimoto Thyroiditis Patients

Aims: To Explore the role of apoptosis in pathogenesis and clinical manifestations of hashimoto thyroiditis (HT) through studying the relationship between peripheral blood concentration of apoptosis factors and thyroid function and related antibodies. Methods: Overall, we recruited 120 cases, including 90 female HT patients who are newly diagnosed and had not accepted any treatment and another 30 healthy controls. The exclusion criteria were current diagnosis or history of severe infections, diabetes, kidney disease and cardiovascular disease, and other autoimmune diseases as well as regular use of any medication. All patients were divided into four groups according to the thyroid function: normal group (group A: n=30), subclinical hypothyroidism group (group B: n=30), hypothyroidism group (group C: n=30). In addition, 30 healthy controls (group D: n=30). Serum B cell lymphoma-2 (Bcl-2), Bcl-2-Associated X (Bax) and Cytochrome C levels were determined by ELISA. Results: The correlation analysis result of Bax levels among four groups was F = 73.56, P < 0.0001, and Bax level of group B was higher than group A and group D, group C higher than that of group B(P < 0.05); Bcl-2 difference was statistically significant, F = 46.01, P < 0.0001, and group C lower than that of group A and group B, group D was higher than group A and group B( P < 0.05); Cytc of four groups was statistically significant difference, F = 141.58, P < 0.0001, and no statistically significant difference between group A and group D. Bax was negatively correlated with FT3 and FT4(r=-0.7057,-0.7177), which was positively correlated with TSH(r=0.6659), all P < 0.05. Bcl-2 was positively correlated with FT3 and FT4(r=0.5496,0.5596), which was negatively correlated with TSH (r=-0.5423), all P < 0.05; Cytc was negatively correlated with FT3 and FT4(r=-0.7027, -0.7733), which was positively correlated with TSH (r=0.7348), all P < 0.05. Bax was positively correlated with TgAb and TPOAb (r=0.4197,0.3020), both P < 0.05; Bcl-2 was negatively correlated with TgAb and TPOAb (-0.4633, -0.4232), both P < 0.05; Cytc was positively correlated with TgAb and TPOAb(r= 0.5816,0.2132 ), both P < 0.05. Conclusion: Bax and Cytc are positively correlated with thyroid antibody and hypothyroidism in HT patients, while Bcl-2 is negatively correlated with thyroid antibody and hypothyroidism in HT patients. Thus, apoptosis may be a thyroid function related pathogenesis of HT.

A Study to Evaluate ID-085 in People With Mild, Moderate, and Severe Kidney Disease

A Study to Evaluate ID-085 in People With Mild, Moderate, and Severe Kidney Disease

Drug-Induced Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey

Background: Acute kidney injury (AKI) is a severe kidney disease. Drug-induced AKI (D-AKI) is one type of AKI, which is difficult to be diagnosed. The incidence of D-AKI in China has rarely been studied. This study aims to explore the disease burden, related drugs and diagnosis status of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in mainland China. Suspected AKI was screened based on serum creatinine changes according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury and patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. D-AKI was firstly evaluated by pharmacists using Naranjo Adverse Drug Reaction Probability Scale and further confirmed by nephrologists through carefully reviewing the medical records. Findings: Altogether 280,255 hospitalized patients were screened and 1960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as D-AKI (37.50%, 735/1960) with a hospital mortality rate of 13.88% and 54.34% of the survivors not achieving full renal recovery. 1642 drugs were related to AKI in these 735 D-AKI patients. Anti-infectives (34.35%, 564/1642), diuretics (21.80%, 358/1642) and proton pump inhibitors (PPIs) (10.48%, 172/1642) were the top 3 types of drugs relavent to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitutes and carbapenems related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Interpretation: In China, D-AKI has caused a substantial medical burden. Chinese pharmacists and nephrologists should bear the major responsibility of leading the campaign of managing D-AKI. Funding Statement: This study is supported by Medical Policy and Administration Department, National Health and Family Planning Commission of China, 2015. The National Natural Science Foundation of China (No.91742205 and No.81625004), the Beijing Young Scientist Program (BJJWZYJH01201910001006), and Peking University Clinical Scientist Program by the Fundamental Research Funds for the Central Universities. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of Xuanwu Hospital of Capital Medical University.

Predictors of NOAC versus VKA use for stroke prevention in patients with newly diagnosed atrial fibrillation: Results from GARFIELD-AF

A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored. Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ± antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016. The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP. GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome.

UPAR isoform 2 forms a dimer and induces severe kidney disease in mice.

Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived circulating signaling molecule that has been implicated in chronic kidney disease, such as focal segmental glomerulosclerosis (FSGS). Typically, native uPAR (isoform 1) translates to a 3-domain protein capable of binding and activating integrins, yet the function of additional isoforms generated by alternative splicing is unknown. Here, we characterized mouse uPAR isoform 2 (msuPAR2), encoding domain I and nearly one-half of domain II, as a dimer in solution, as revealed by 3D electron microscopy structural analysis. In vivo, msuPAR2 transgenic mice exhibited signs of severe renal disease characteristic of FSGS with proteinuria, loss of kidney function, and glomerulosclerosis. Sequencing of the glomerular RNAs from msuPAR2-Tg mice revealed a differentially expressed gene signature that includes upregulation of the suPAR receptor Itgb3, encoding β3 integrin. Crossing msuPAR2-transgenic mice with 3 different integrin β3 deficiency models rescued msuPAR2-mediated kidney function. Further analyses indicated a central role for β3 integrin and c-Src in msuPAR2 signaling and in human FSGS kidney biopsies. Administration of Src inhibitors reduced proteinuria in msuPAR2-transgenic mice. In conclusion, msuPAR2 may play an important role in certain forms of scarring kidney disease.

Recombinant Production of MFHR1, A Novel Synthetic Multitarget Complement Inhibitor, in Moss Bioreactors.

The human complement system is an important part of the immune system responsible for lysis and elimination of invading microorganisms and apoptotic body cells. Improper activation of the system due to deficiency, mutations, or autoantibodies of complement regulators, mainly factor H (FH) and FH-related proteins (FHRs), causes severe kidney and eye diseases. However, there is no recombinant FH therapeutic available on the market. The first successful recombinant production of FH was accomplished with the moss bioreactor, Physcomitrella patens. Recently, a synthetic regulator, MFHR1, was designed to generate a multitarget complement inhibitor that combines the activities of FH and the FH-related protein 1 (FHR1). The potential of MFHR1 was demonstrated in a proof-of-concept study with transiently transfected insect cells. Here, we present the stable production of recombinant glyco-engineered MFHR1 in the moss bioreactor. The key features of this system are precise genome engineering via homologous recombination, Good Manufacturing Practice-compliant production in photobioreactors, high batch-to-batch reproducibility, and product stability. Several potential biopharmaceuticals are being produced in this system. In some cases, these are even biobetters, i.e., the recombinant proteins produced in moss have a superior quality compared to their counterparts from mammalian systems as for example moss-made aGal, which successfully passed phase I clinical trials. Via mass spectrometry-based analysis of moss-produced MFHR1, we now prove the correct synthesis and modification of this glycoprotein with predominantly complex-type N-glycan attachment. Moss-produced MFHR1 exhibits cofactor and decay acceleration activities comparable to FH, and its mechanism of action on multiple levels within the alternative pathway of complement activation led to a strong inhibitory activity on the whole alternative pathway, which was higher than with the physiological regulator FH.

Optimizing antiretroviral regimens in chronic kidney disease.

To identify recent data that inform the management of individuals with HIV and chronic kidney disease. Several nonnucleoside reverse transcriptase, protease, and integrase strand transfer inhibitors inhibit tubular creatinine secretion resulting in stable reductions in creatinine clearance of 5-20 ml/min in the absence of other manifestations of kidney injury. Progressive renal tubular dysfunction is observed with tenofovir disoproxil fumarate in clinical trials, and more rapid decline in estimated glomerular filtration rate in cohort studies of tenofovir disoproxil fumarate and atazanavir, with stabilization, improvement or recovery of kidney function upon discontinuation. Results from clinical trials of tenofovir alafenamide (TAF) in individuals with chronic kidney disease suggest that TAF is well tolerated in those with mild to moderate renal impairment (creatinine clearance >30 ml/min) but results in very high tenofovir exposures in those on haemodialysis. Standard antiretroviral regimens remain appropriate for individuals with normal and/or stable, mildly impaired kidney function. In those with chronic kidney disease or progressive decline in estimated glomerular filtration rate, antiretrovirals with nephrotoxic potential should be avoided or discontinued. Although TAF provides a tenofovir formulation for individuals with impaired kidney function, TAF is best avoided in those with severe or end-stage kidney disease.

Hydrocephalus in a rat model of Meckel Gruber syndrome with a TMEM67 mutation

Transmembrane protein 67 (TMEM67) is mutated in Meckel Gruber Syndrome type 3 (MKS3) resulting in a pleiotropic phenotype with hydrocephalus and renal cystic disease in both humans and rodent models. The precise pathogenic mechanisms remain undetermined. Herein it is reported for the first time that a point mutation of TMEM67 leads to a gene dose-dependent hydrocephalic phenotype in the Wistar polycystic kidney (Wpk) rat. Animals with TMEM67 heterozygous mutations manifest slowly progressing hydrocephalus, observed during the postnatal period and continuing into adulthood. These animals have no overt renal phenotype. The TMEM67 homozygous mutant rats have severe ventriculomegaly as well as severe polycystic kidney disease and die during the neonatal period. Protein localization in choroid plexus epithelial cells indicates that aquaporin 1 and claudin-1 both remain normally polarized in all genotypes. The choroid plexus epithelial cells may have selectively enhanced permeability as evidenced by increased Na+, K+ and Cl− in the cerebrospinal fluid of the severely hydrocephalic animals. Collectively, these results suggest that TMEM67 is required for the regulation of choroid plexus epithelial cell fluid and electrolyte homeostasis. The Wpk rat model, orthologous to human MKS3, provides a unique platform to study the development of both severe and mild hydrocephalus.

Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka.

A kidney disease of unknown cause is common in Sri Lanka's lowland (dry) region. Detailed clinical characterizations of patients with biopsy-proven disease are limited, and there is no current consensus on criteria for a noninvasive diagnosis. We designed a prospective study in a major Sri Lankan hospital servicing endemic areas to ascertain pathologic and clinical characteristics of and assess risk factors for primary tubulointerstitial kidney disease. We used logistic regression to determine whether common clinical characteristics could be used to predict the presence of primary tubulointerstitial kidney disease on kidney biopsy. From 600 new patients presenting to a tertiary nephrology clinic over the course of 1 year, 87 underwent kidney biopsy, and 43 (49%) had a biopsy diagnosis of primary tubulointerstitial kidney disease. On detailed biopsy review, 13 (30%) had evidence of moderate to severe active kidney disease, and six (15%) had evidence of moderate to severe chronic tubulointerstitial kidney disease. Patients with tubulointerstitial kidney disease were exclusively born in endemic provinces; 91% spent a majority of their lifespan there. They were more likely men and farmers (risk ratio, 2.0; 95% confidence interval, 1.2 to 2.9), and they were more likely to have used tobacco (risk ratio, 1.7; 95% confidence interval, 1.0 to 2.3) and well water (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). Three clinical characteristics-age, urine dipstick for protein, and serum albumin-could predict likelihood of tubulointerstitial kidney disease on biopsy (model sensitivity of 79% and specificity of 84%). Patients referred for kidney biopsy despite comorbid diabetes or hypertension did not experience lower odds of tubulointerstitial kidney disease. A primary tubulointerstitial kidney disease occurs commonly in specific regions of Sri Lanka with characteristic environmental and lifestyle exposures.

Uremic frost- A rare skin manifestation of severe kidney disease

Uremic frost is a rare dermatological manifestation of severe azotemia. It is rarely seen today because of early dialytic intervention. It occurs when high concentration of urea and other nitrogenous waste products accumulate in the sweat and then crystallizes as deposit on the skin after evaporation in a process called uridrosis or urinous sweat. Its a sign of impending renal failure and portends bad prognosis. Involvement of urea transporters may have a role in its development. Damage to the cutaneous microvasculature, eccrine sweat and sebaceous glands may be responsible for the high level of urea accumulation on skin. The test to analyze that the crystalline material is urea or nitrogenous waste products, the scrapings of the sample can be dilutad in normal saline and then tested for elevated urea nitrogen level. No specific therapy except correcting the underlying etiology

Sodium Fluctuations and Mortality in a General Hospitalized Population

Background/Aims: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. Methods: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. Results: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend <0.001) irrespective of severity of dysnatremia (HR 2.34, 95% CI 1.55, 3.54, p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). Conclusions: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.

Risk factors for ischemic stroke and stroke subtypes in patients with chronic kidney disease.

The aim of this study was to compare ischemic stroke subtypes with the effects of risk factors, the relationship between grades of kidney disease and the severity of stroke subtypes. The current study was designed retrospectively and performed with data of patients who were hospitalised due to ischemic stroke. We included 198 subjects who were diagnosed with ischemic stroke of Grade 3 and above with chronic kidney disease. In our study were reported advanced age, coronary artery disease, moderate kidney disease as the most frequent risk factors for cardioembolic etiology. Hypertension, hyperlipidemia, smoking and alcohol consumption were the most frequent risk factors for large-artery disease. Female sex and anaemia were the most frequent risk factors for small-vessel disease. Dialysis and severe kidney disease were the most frequent risk factors in unknown etiologies, while male sex, diabetes mellitus, prior stroke and mild kidney disease were the most frequent risk factors for other etiologies. National Institute of Health Stroke Scale (NIHSS) scores were lower for small-vessel disease compared with other etiologies. This relation was statistically significant (p=0.002). In order to improve the prognosis in ischemic stroke with chronic kidney disease, the risk factors have to be recognised and the treatment options must be modified according to those risk factors.