Chronic Interstitial Nephropathy Research Articles

#3034 Therapeutic compliance: another challenge for patients on chronic hemodialysis

Abstract Background and Aims Therapeutic compliance corresponds to the degree of concordance between the patient's behavior and the recommendations of his doctor. Non-adherence to treatment predispose to high risk of mortality and increases health costs. The objective of our study was to assess the level of compliance in chronic hemodialysis patients and to identify the predictive factors of poor compliance. Method A cross-sectional study was conducted in the hemodialysis center at Taher Sfar Hospital in Mahdia. Medication adherence was assessed using a “compliance assessment test” quiz comprising six questions to which the patient must answer yes or no. Results Sixty-one patients were enrolled. The mean age was 50 ± 13 years (26 - 79 years) with a sex ratio M/F of 1.27. The patients have diabetes mellitus and hypertension in 35% and 68% of cases. They were dialyzed for a long duration (37 ± 15 months) that reaches a maximum of 280 months. The main initial nephropathies were diabetic nephropathy (35.5%) and chronic interstitial nephropathy (23.5%). Adherence was poor in 16.9 % of patients, average in 55.9% of patients while 27.1% were good adherents. Polymedication and missing of treatment were the leading causes of non-adherence. In univariate analyses, the socio-economic level affected significantly the compliance in elderly group as well as high comorbidity score (Charlson) (p<0.04) and diabetes status (p=0.04). No significant difference was found between elderly and young group in term of compliance to treatment. Conclusion Compliance is a dynamic behavior that is difficult to predict and requires constant monitoring. In our hemodialysis center it turned out to be good; we must insist on the therapeutic education of patients and minimize the list to the necessary.

CARDIOVASCULAR COMPLICATIONS AFTER CADAVERIC RENAL TRANSPLANTATION

Objective: Renal transplantation is the treatment for end-stage renal disease. Cadaveric donor renal transplantation (CDRT) is still uncommon in Tunisia, constituting less than 20% of total renal transplants. The aim of our study was to evaluate the results and cardiovascular complications in our center Design and method: A retrospective analysis of 30 CDRT was performed between November 1995 and December 2018. Data analysis included. age, gender, cold ischemia time, graft function graft function, dialysis requirements dialysis requirements, rejection episodes rejection, infectious episodes, new onset diabetes after transplantation (NODAT), hypertension and cardiovascular events Results: Thirty patients underwent CDRT among 172 renal transplants performed in our unit. Among the donors, there were 23 males and 7 females, with a mean age of 32 ± 9 years. All transplants were blood group compatible with 3 HLA matches in the majority of cases (45%). The mean age of the recipients was 34 ± 9 years. Chronic glomerulonephritis (40%) and chronic chronic interstitial nephropathy (32%) represented the main type of native renal disease. 88.5% of the patients were hemodialysis before transplantation and the median time to transplantation on dialysis was dialysis was eight years. The mean nadir of creatinine was 108 ± 27 μmol/l. Two biopsies showed acute tubular injury, four patients had acute rejection and two patients had allograft nephropathy allograft nephropathy with one case of segmental and focal hyalinosis. segmental and focal hyalinosis. The major infectious complication was a cytomegalovirus cytomegalovirus infection (33.3%) followed by a urinary tract infection (23.8%). Regarding metabolic complications metabolic complications, NODAT and hypertension were observed in three and four patients respectively. Two patients presented an acute coronary syndrome treated with medical therapy. Five patients returned to dialysis. The rest (57.7%) have been followed up regularly in our consultation so far over a period of 87 months (range 16-209 months). Conclusions: CDRT is not common in our center, but the analysis shows good results and provides encouraging data that support broadening the criteria for potential donors eligible for organ donation especially in the face of increasing organ shortages. Cardiovascular complications are not as common

Emphysematous cystitis in a renal transplant recipient

Emphysematous cystitis is a rare entity characterized by gas inside the bladder and in its wall on CT, the gold standard to establish the diagnosis. Few renal transplant recipients have reported few cases, and none of them had associated diabetes over the last ten years. We report the case of a 64-year-old female who had a history of type 2 diabetes mellitus and who presented emphysematous cystitis nine years after her kidney transplant for chronic interstitial nephropathy. Abbreviations: CBEU: cytobacteriological examination of urine.; CT: Computed Tomography; CECT: Contrast-enhanced computed tomography; CBEU:Cytobacteriological examination of urine

POS-522 EARLY VERSUS LATE DIALYSIS: TIMING AND MORTALITY

Chronic kidney disease remains one of the diseases with a high cardiovascular morbidity andmortality, especially when approaching the end stage. The correct timing of dialysis initiation remains a controversial issue until now. The aim of this study is to compare early and late dialysis andtheir impact on mortality. This is a retrospective study. We collected sociodemographic, clinical and biological data from the medical records of patients who reached the end stage, divided into two groups : early HDP hemodialysis with a glomerular filtration rate (GFR > 7 ml/min) and late HDT hemodialysis (GFR ≤ 7ml/min). Our study included 149 patients of whom 66 were in the HDT group. The mean age was 59.38 yearsand 64.27 years in the HDT and HDP groups respectively. The mean GFR in the HDT and HDP group was 5.4 ml/min and 9.8 ml/min. The percentages of hypertension, diabetes and coronaryi nsufficiency were respectively in HDT and HDP : 41.35%, 36.47%, 41.38% and 58.65%, 63.53%,58.62%. The main etiologies of CKD were : diabetes (26.56% HDT ; 20.73% HDP), chronic interstitial nephropathy (18.75% HDT ; 23.17% HDP), vascular nephropathy (7.8% HDT ; 4.88% HDP), chronic glomerular nephropathy (9.37% HDT ; 12.19% HDP) and indeterminate (37.5% HDT ; 30.49% HDP) Mortality in the HDT group was 34.85% (n=23) and in the HDP group 48.19% (n=40). There was no significant difference in mortality between the 2 groups (p=0.1014). In our study, mortality was slightly higher in HDP group than among HDT group, but was not significant, which requires larger studies spread over time to confirm or disprove this result.

POS-784 VESICO-URETERAL REFLUX POST RENAL TRANSPLANTATION,A DESCRIPTIVE STUDY

The vesico-ureteral reflux (VUR) is a urological complication frequently encountered in post renal transplantation (RT), reaching 10 to 15% in some series. The objective of our study is to determine the prevalence of VUR after RT, to study the characteristics of the affected population and the impact on graft function. A retrospective descriptive study of all kidney transplant patients between 2007 and 2018 who were diagnosed with a VUR after RT. The characteristics of the initial nephropathy, the mode of revealing of the reflux, the consequences on renal function and the recurrence of urinary tract infections were studied for each . Among the 209 kidney transplants, 31 patients had a RVU, making it a prevalence of 14,8 %, with a sex ratio of 1,58 : 19 men and 12 women. The mean age at the time of transplantation was 28,33 years old. For initial nephropathy, 22 had chronic interstitial nephropathy (71%) including 8 secondary to reflux nephropathy, 19,4% had a glomerular desease and 3,2 % had a vascular cause. Before transplantation, patients had an average hemodialysis duration of 2.6 years with extremes ranging from a few months to 10 years, 13 patients were already oligo-anuric. As for VUR on graft, it was diagnosed with an average delay of 11.5 months post TR [3 months;36months] in front of recurrent urinary tract infections in 10 patients, pyelocalicial dilation seen on renal ultrasound in 4 cases and unexplained creatinine increase in 6 cases. VUR on renal graft is seen in patients of different sex and age with a variable duration of hemodialysis and residual diuresis, but in post-transplantation, it is the recurrence of urinary tract infections that should make the diagnosis suspected.

POS-366 WHAT DOES A DIABETIC KIDNEY HIDE?

Renal biopsy indications in diabetic patients are limited. We usually tend to biopsy when the diagnosis is doubted or when another diagnosis is suspected. Between 2007 and 2018, 548 patients were diagnosed with diabetic nephropathy (DN) , based on clinical and biological data. However, some patients needed a biopsy. Amongst 548 patients, only 29 have had renal biopsy. The leading symptom motivating the biopsy were hematuria ( 14 cases), then rapidly progressive renal failure (7 cases), renal failure without any proteinuria (3 cases), the absence of diabetic degenerative features (3 cases) and intense nephrotic syndrome (2 cases). All these patients had histological features of diabetic nephropathy. Nevertheless, eighteen (62%) had also non-diabetic renal disease( NDRD) which were acute glomerulonephritis (10 cases) , immunoglobulin A nephropathy (2 cases) , AL amyloidosis (2 cases) , chronic interstitial nephropathy ( 2 cases), acute interstitial nephritis (1 case) and 1 case of membranoproliferative glomerulonephritis. Distinguishing DN from NDRD on clinical facts is not obvious. However their association is not rare. Renal biopsy indications may be enlarged, new DN features may be found, and a better treatment strategy may be launched.

Naturally Acquired Mouse Kidney Parvovirus Infection Produces a Persistent Interstitial Nephritis in Immunocompetent Laboratory Mice.

Mouse kidney parvovirus (MKPV), also known as murine chapparvovirus (MuCPV), is an emerging, highly infectious agent that has been isolated from laboratory and wild mouse populations. In immunocompromised mice, MKPV produces severe chronic interstitial nephropathy and renal failure within 4 to 5 months of infection. However, the course of disease, severity of histologic lesions, and viral shedding are uncertain for immunocompetent mice. We evaluated MKPV infections in CD-1 and Swiss Webster mice, 2 immunocompetent stocks of mice. MKPV-positive CD-1 mice (n = 30) were identified at approximately 8 weeks of age by fecal PCR (polymerase chain reaction) and were subsequently housed individually for clinical observation and diagnostic sampling. Cage swabs, fecal pellets, urine, and blood were evaluated by PCR at 100 and 128 days following the initial positive test, which identified that 28 of 30 were persistently infected and 24 of these were viremic at 100 days. Histologic lesions associated with MKPV in CD-1 (n = 31) and Swiss mice (n = 11) included lymphoplasmacytic tubulointerstitial nephritis with tubular degeneration. Inclusion bodies were rare; however, intralesional MKPV mRNA was consistently detected via in situ hybridization within tubular epithelial cells of the renal cortex and within collecting duct lumina. In immunocompetent CD-1 mice, MKPV infection resulted in persistent shedding of virus for up to 10 months and a mild tubulointerstitial nephritis, raising concerns that this virus could produce study variations in immunocompetent models. Intranuclear inclusions were not a consistent feature of MKPV infection in immunocompetent mice.

Péritonite à Capnocytophaga spp. en dialyse péritonéale automatisée : à propos d’un cas

IntroductionCapnocytophaga spp. is a slow-growing bacterium that forms a part of the normal oral flora of dogs and cats. In peritoneal dialysis, only seven cases have been reported. We report the observation of a case of peritonitis with Capnocytophaga spp. in a patient on peritoneal dialysis who lives with a cat. Case reportA 64-year-old woman with chronic end stage renal disease due to chronic interstitial nephropathy on automated peritoneal dialysis has been admitted for diffuse abdominal pain. The dialysis fluid was cloudy with 11,250 elements/mm3, of leukocytes. Direct examination was negative. The C-reactive protein was 165mg/L. Intraperitoneal probabilistic antibiotic therapy was initiated 1g of cefazolin and 1g of ceftazidime per day. After eight days, aerobic culture was negative, the anaerobic one was positive to gram negative bacilli, but the identification could not be possible with MALDI-TOF mass spectrometry. Antibiotic therapy was continued by ceftazidime for 21 days. The evolution was marked by the improvement of the clinical and biological state of the patient. The germ was finally identified using the genomic 16S rRNA sequencing technique. This is Capnocytophaga spp. Investigation then revealed that the patient's cat sometimes entered her room at the time of connection of peritoneal dialysis. ConclusionThe case of our patient once again reveals the diagnostic difficulties posed by Capnocytophaga spp. Innovative techniques, such as MALDI-TOF-MS or genomic sequencing of ribosomal RNA, should be further used in peritoneal dialysis in the diagnosis of peritonitis.

P0294WHEN DO WE HAVE TO SUSPECT THAT A PREECLAMPSIA MASKS A GLOMERULOPATHY?

Abstract Background and Aims Between the 2-8% of pregnancies suffer preeclampsia (PE). In the literature, there have been reported cases of glomerulopathy debuted by pregnancy (GDP) which are initially missdiagnosed as PE. These cases are unusual and not well-defined. We aimed to evaluate clinical and analytical factors that allow us to suspect that a PE masks a GDP. Method Retrospective study that included pregnant patients with a postpartum histological diagnosis of glomerulopathy who had been missdiagnosed as PE during pregnancy. We compared them with patients who suffered PE with full recovery after childbirth. We evaluate demographic variables of pregnant women and newborns, clinical variables related to pregnancy and childbirth, blood pressure (BP) and analytical variables before pregnancy and postpartum (serum creatinine (sCrea), estimated glomerular filtration rate by CKD-EPI equation (eGFR), serum uric acid (sUA), ratio of urine protein to creatinine (UPCR)). Results Thirty patients were included in the study ,10 patients with a postpartum histological diagnosis of glomerulopathy who had been diagnosed as PE during the pregnancy and 20 patients with a diagnosis of PE without GDP, baseline characteristics are described in attached table. Glomerulopathy was diagnosis through renal biopsy, main indication of renal biopsy was the persistence of proteinuria and/or sediment abnormalities after 4 months of childbirth. The diagnoses were: IgA nephropathy (3, 33.3%), focal and segmental hyalinosis (2, 22.2%), X-linked Alport syndrome (2, 22.2%), diabetic nephropathy (1, 11.1%), lupus nephritis (1, 11.1%) and chronic interstitial nephropathy (1, 11.1%). Pregnant women with GDP showed higher prevalence of smoking habit and major value of sCrea and sUA (figure). Regarding to pregnancy factors, patients with GDP had significant higher prevalence of primiparous gestation (100% vs 40%, p=0.002), twin gestation (20% vs 0%, p=0.03), premature newborn (50% vs 15%, p=0.01) and higher weight gain during pregnancy (13.9±5.8 vs 9.5±3.6 kg, p=0.01). Furthermore, in the postpartum data we objected a higher value of systolic/diastolic BP (145.6±10.3 / 89.4±12.1 vs 128.5±10.0 / 80.0±6.3 mmHg, p<0.05), sCrea (0.83±0.3 vs 0.54±0.2 mg/dl, p=0.02), sUA (5.8±1.3 vs 3.4±0.8 mg/dl, p<0.001) and UPCR (3046 [613-4179] vs 802 [281-948] mg/g, p=0.05) in patient with NPD. Conclusion Our results suggest that clinical and analytical variables in pregnancy and post-partum allow clinicians suspect a glomerulopathy in the setting of PE. Patients diagnosed as PE who develop GDP had higher prevalence of smoking habit, primiparous gestation, twin gestation and premature newborns. In addition, they also have higher weight gain during pregnancy, worse renal function and major sUA before pregnancy and after childbirth, and major UPCR and BP after childbirth; compared with patients with PE and full recovery after childbirth.

P0126RENAL TRANSPLANT PATIENTS UNDER CALCINEURIN INHIBITOR THERAPY RAPIDLY ACQUIRE AN ABERRANT LYSOSOMAL LESION IN PROXIMAL TUBULAR CELLS

Abstract Background and Aims Calcineurin inhibitor therapy has changed the field of (renal) transplantation by considerably prolonging graft survival. Yet, all immunosuppressive calcineurin inhibitors are nephrotoxic that eventually contribute to complete scarring of the renal allograft. In renal biopsy analysis many histopathological features have been considered indicative of CNI nephrotoxicity, i.e. striped fibrosis, vascular hyalinosis, isometric tubular vacuolization, glomerulosclerosis, cellular infiltration and tubular atrophy, however, all are rather aspecific and can be secondary to many other causes. During the course of evaluating the specificity of a recently discovered proximal epithelial lysosomal lesion (i.e. multiple enlarged (>1,2µm) dysmorphic lysosomes containing dispersed electron dense non-membrane bound aggregates) in patients with Chronic Interstitial Nephropathy in Agricultural Communities (CINAC), we observed it to be present in renal transplant patients treated with cyclosporine or tacrolimus. Here, we test the hypothesis whether this lysosomal lesion is acquired during CNI therapy. Method A retrospective transmission electron microscopic analysis was performed to evaluate the presence of the typical lysosomal lesion on the following biopsies from renal transplant patients: 20 deceased donor implantation biopsies; 5 living donor implantation biopsies. For another 10 additional deceased donor renal allograft recipients, we evaluated implantation as well as protocol biopsies taken after 6 and 12 months of CNI treatment that started immediately after transplantation. Also included were 24 indication biopsies of CNI treated renal transplants. Results Of the total set of implantation biopsies (n=35), 2 (6%) were positive for the aberrant lysosomal phenotype on EM, whereas in the protocol and indication biopsies prevalence of the lesion was considerably higher ranging between 56% (protocol) and 80% (indication) of cases. Conclusion CNI therapy is associated with the fairly rapid appearance of a particular proximal tubular lysosomal phenotype observable on EM, that was not (or rarely) present at implantation. Whether this lesion is related to CNI toxicity and indicative for the outcome for the graft and/or patient survival after renal transplantation has to be investigated in a prospective trial.

The Case | Severe acute hypocalcemia in a patient on hemodialysis

A 56-year-old Caucasian man on maintenance hemodialysis for 5 years for end-stage kidney disease secondary to lithium-induced chronic interstitial nephropathy presented with acute and severe weakness of the 4 limbs.

The link between phenotype and fatty acid metabolism in advanced chronic kidney disease.

The kidney plays a central role in elimination of metabolic waste products and regulation of low-molecular weight metabolites via glomerular filtration, tubular secretion and reabsorption. Disruption of these processes results in profound changes in the biochemical milieu of the body fluids, which contribute to complications of chronic kidney disease (CKD) by inducing cytotoxicity and inflammation. Insight into the changes of the composition of metabolites and dysregulation of target genes and proteins enhances the understanding of the pathophysiology of CKD and its complications, and the development of novel therapeutic strategies. Chronic interstitial nephropathy is a common cause of CKD. The present study was designed to determine the effect of chronic interstitial nephropathy on the composition of serum metabolites and regulation of oxidative, inflammatory, fibrotic and cytoprotective pathways. Male Sprague-Dawley rats were randomized to the CKD and control groups ( n = 8/group). CKD was induced by administration of adenine (200 mg/kg body weight/day) by oral gavage for 3 weeks. The control group was treated with the vehicle alone. The animals were then observed for an additional 3 weeks, at which point they were sacrificed and kidney and serum samples were collected. Serum metabolomic and lipidomic analyses were performed using ultra-performance liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry. Kidney tissues were processed for histological and molecular biochemical analyses. CKD rats exhibited increased plasma urea and creatinine concentrations, renal interstitial fibrosis, tubular damage and up-regulation of pro-inflammatory, pro-oxidant and pro-fibrotic pathways. Comparison of serum from CKD and control rats revealed significant differences in concentrations of amino acids and lipids including 33 metabolites and 35 lipid species. This was associated with marked abnormalities of fatty acid oxidation, and γ-linolenic acid and linoleic acid metabolism in CKD rats. Logistic regression analysis identified tetracosanoic acid, docosatrienoic acid, PC(18:3/14:1) and l -aspartic acid, tetracosanoic acid and docosatrienoic acid as novel biomarkers of chronic interstitial nephropathy. Advanced CKD in rats with adenine-induced chronic interstitial nephropathy results in profound changes in the serum metabolome, activation of inflammatory, oxidative and fibrotic pathways, and suppression of cytoprotective and antioxidant pathways.

A comparison of cystatin C concentrations between patients with chronic interstitial nephritis and glomerular diseases.

Cystatin C have shown to be a renal function parameter with higher sensitivity and specificity than serum creatinine. In tubular diseases, cystatin C degradation and an increase in its urinary elimination would be observed. We have tried to define if different kinds of kidney diseases may significantly affect the serum levels of cystatin C. Four hundred and four patients were studied: 249 men and 155 women, mean age was 64.3±10.1years. Patients were classified into three groups: (1) Chronic interstitial nephropathy (CIN), (2) Glomerular nephropathy (GN), and (3) Non- CKD patients (control). GFR was estimated though the CKD-EPI equation and the Hoek formula. Median of serum creatinine levels was higher in CIN group than in GN and control groups. Median cystatin C levels were lower in control group compared with CIN and GN groups. No significant differences were found between CIN group and GN group. Nevertheless, the cystatin/creatinine rate was lower in the CIN group patients (0.94, 0.81-1.11) than in the GN group (1.02,I 0.85-1.25) as well as the control group (1.02, I 0.88-1.20). The cystatin C-estimated GFR/creatinine-estimated GFR rate was higher in the CIN group (1.18, 1.03-1.36) than in the GN patients (1.03, 0.88-1.21) and control ones (1.07, 0.88-1.20). Patients with CIN had lower serum levels of cystatin C defined as cystatin C/creatinine rate when they were compared with GN subject and control ones. In the same way, the index between cystatin C-estimated GFR and creatinine-estimated GFR was higher in CIN patients.

Ochratoxin A: 50 Years of Research.

Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans.

A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial Nephritis.

Karyomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy characterized by tubulointerstitial nephritis and formation of enlarged nuclei in the kidneys and other tissues. We recently reported that recessive mutations in the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans. FAN1 is a major component of the Fanconi anemia-related pathway of DNA damage response (DDR) signaling. To study the pathogenesis of KIN, we generated a Fan1 knockout mouse model, with abrogation of Fan1 expression confirmed by quantitative RT-PCR. Challenging Fan1-/- and wild-type mice with 20 mg/kg cisplatin caused AKI in both genotypes. In contrast, chronic injection of cisplatin at 2 mg/kg induced KIN that led to renal failure within 5 weeks in Fan1-/- mice but not in wild-type mice. Cell culture studies showed decreased survival and reduced colony formation of Fan1-/- mouse embryonic fibroblasts and bone marrow mesenchymal stem cells compared with wild-type counterparts in response to treatment with genotoxic agents, suggesting that FAN1 mutations cause chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in the physiologic response of kidney tubular cells to DNA damage, which contributes to the pathogenesis of CKD. Moreover, Fan1-/- mice provide a new model with which to study the pathomechanisms of CKD.

Clinical Scenarios in Chronic Kidney Disease: Chronic Tubulointerstitial Diseases.

Chronic tubulointerstitial diseases are a common final pathway toward chronic renal failure regardless the primary damage (glomerular, vascular or directly the tubulointerstitium). Chronic tubulointerstitial nephritis (CTN) is characterized by interstitial scarring, fibrosis and tubule atrophy, resulting in progressive chronic kidney disease. Most frequent causes of CTN are drugs, heavy metals, obstructive uropathy, nephrolithiasis, reflux disease, immunologic diseases, neoplasia, ischemia, metabolic diseases, genetics and miscellaneous. At ultrasound (US), kidneys' morphological aspect is similar in all forms of chronic interstitial nephropathy and only chronic pyelonephritis with or without reflux shows distinguishing characteristics. In interstitial nephropathy, kidneys' profiles are finely irregular and corticomedullary differentiation is altered because of a diffused hyperechogenicity. The only indirect sign of chronic interstitial damage can be derived from the value of intrarenal resistive indexes that hardly overcome 0.75. US is mandatory in clinical chronic pyelonephritis work-up because it provides information on kidney's diameter and on growth nomogram in children. Renal profiles can be more or less altered depending on the number of cortical scars and the presence of pseudonodular areas of segmental compensatory hypertrophy. In the early stages, US diagnosis of renal tuberculosis is difficult because parenchymal lesions are non-specific. US sensitivity in the diagnosis of hydronephrosis is very high, close to 100% and, finally, US is the first choice imaging technique in the diagnosis of urinary lithiasis.

Prevalence and determinants of the metabolic syndrome among subjects with advanced nondiabetes-related chronic kidney disease in Gran Canaria, Spain

Background The relationship between the metabolic syndrome and mild chronic kidney disease (CKD) has been extensively studied. This study was aimed to estimate the prevalence and factors associated with the metabolic syndrome among subjects with advanced stages of nondiabetes-related CKD. Methods Study population was composed of incident patients with advanced CKD not related to diabetes in a tertiary hospital from Gran Canaria (Spain) since February 2011 to December 2014. Participants fulfilled a survey questionnaire and underwent physical examination and biochemical evaluation. Results The sample was composed of 167 subjects (mean age 63.9 ± 13.7 years; estimated glomerular filtration rate 21.9 ± 6.6 mL/min/1.73 m2). The prevalence of the metabolic syndrome was 68.9% (65.2% in men and 73.3% in women). Highest rates were observed in groups with chronic interstitial nephropathy (80%), CKD of uncertain etiology (76.7%) and CKD related to vascular causes (76.2%). Subjects with metabolic syndrome were older, had higher values of C-reactive protein and more often reported to have first-degree relatives with diabetes and to be physically inactive. In multivariate analyses, age (OR: 1.034 [CI 95%: 1.004–1.065]; p = 0.024) and family history of diabetes (OR: 2.550 [1.159–5.608]; p = 0.020) were independently associated with the metabolic syndrome. Conclusions The prevalence of the metabolic syndrome among subjects with advanced nondiabetes-related CKD is high, and greater than that observed in general Canarian population of similar age groups. Age and family history of diabetes are the two factors more strongly associated with the metabolic syndrome in this population.

MicroRNA-205 inhibits renal cells apoptosis via targeting CMTM4.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles in kidney development, homeostasis and disease, and participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). In the present study, we elucidated the role of microRNA 205 (miR-205) in cisplatin-induced renal cell apoptosis and explored the molecular mechanisms. The chronic interstitial nephropathy rat model was induced, and the miRNA expression profile in the kidney cells from rats with CKD was screened. Cisplatin-induced apoptosis in normal renal HK-2 cells was evaluated using flow cytometry, and regulation of miR-205 on target gene was validated using luciferase assay, western blot and real time PCR assays. We found that miR-205 expression was significantly decreased in the cells from kidney of CKD rat (P<0.01). Our data showed that when miR-205 was overexpressed or silenced using the mimic or inhibitor, the percentages of apoptotic cells were suppressed or increased significantly (P<0.05), respectively. Moreover, we have identified CMTM4 gene, which is involved in cell proliferation and apoptosis, as a novel target for miR-205. In addition, miR-205 could inhibit apoptosis by binding to the 3'UTR of CMTM4 mRNA and inhibiting its transcriptional activity. This study elucidated that miR-205 plays an important role in the regulation of apoptosis in renal cells, suggesting a potential therapeutic target to hinder CKD development.

Chronic Kidney Disease Results in Deficiency of ABCC6, the Novel Inhibitor of Vascular Calcification

Background: Chronic kidney disease (CKD) is associated with arterial medial calcification which plays a major role in the pathogenesis of cardiovascular disease in this population. Several factors are known to promote soft tissue and accelerated arterial calcification in CKD including systemic inflammation, altered calcium and phosphate homeostasis, hypertension, and deficiency of endogenous calcification inhibitors. The ABCC6 transporter (ATP-binding cassette subfamily C number 6), also known as multidrug resistance-associated protein 6 (MRP6), is highly expressed in the liver and kidney. Mutation of ABCC6 results in pseudoxanthoma elasticum, an inherited disorder characterized by arterial and soft tissue calcification. Given the prevalence of arterial medial calcification in CKD, the present study was undertaken to test the hypothesis that CKD may lead to acquired ABCC6 deficiency. Methods: CKD was induced via 5/6 nephrectomy in male Sprague-Dawley rats and by adenine-containing diet to cause chronic interstitial nephropathy in female DBA/2J mice. Sham-operated rats and mice fed regular diet served as controls. Liver and kidney tissues were harvested and processed for ABCC6 protein and mRNA analysis. Results: ABCC6 protein levels were significantly reduced in the liver and kidney tissues from CKD rats and mice. However, ABCC6 mRNA levels were unchanged, pointing to post-transcriptional or post-translational mechanisms for the observed ABCC6 deficiency. Additionally, plasma levels of the calcification inhibitor fetuin-A were significantly decreased in CKD animals compared to controls. Conclusions: CKD results in acquired ABCC6 transporter deficiency. To our knowledge this abnormality has not been previously reported and may contribute to CKD-associated vascular and soft tissue calcification.

AB0936 Renal Involvement in Sarcoidosis: A Study of 50 Cases

BackgroundClinically important renal involvement occasionally occurs in sarcoidosis. Renal manifestations include abnormal calcium metabolism, nephrolithiasis and nephrocalcinosis, and acute interstitial nephritis with or without granuloma formation.ObjectivesTo analyze the pattern of...