Nephropathic Patients Research Articles

Role of biomarkers of inflammation and MRI technique for the early detection of cystinosis-associated myopathy

BackgroundCystinosis is an autosomal recessive lysosomal storage disorder caused by cystine crystals accumulation within lysosomes resulting in multi-organ dysfunction. Infantile nephropathic cystinosis is the most common phenotype of the disease. Cystinosis distal myopathy was first described in 1994 with a 24% prevalence in cystinosis adult patients.MethodsWe prospectively evaluated the clinical, biochemical, and radiological data of 22 nephropathic cystinosis pediatric patients from 19 unrelated families (17 males and 5 females, their ages 105.7 ± 41.5 months) recruited at the cystinosis clinic at Cairo University Children’s Hospital. Biochemical assessment included several inflammatory biomarkers, such as CRP, ESR, chitotriosidase, and galectin-3. We further performed conventional MRI for the muscles of both upper and lower limbs for potential detection of early myopathic involvement. We compared these findings with 44 CKD children as pathological controls and 22 healthy pediatric controls.ResultsClinically, no evidence of neuromuscular involvement was detected in our cystinosis pediatric cohort. Chitotriosidase was elevated significantly in cystinosis patients compared to CKD controls. Regarding MRI, morphologically, there were no significant differences between the muscles of cystinosis patients and healthy controls.ConclusionA significantly higher chitotriosidase activity in cystinosis patients seems to better represent the overall disease burden and cannot be linked to neuromuscular involvement. MRI findings in muscles of the cystinosis cohort are not striking and indicate no early changes at a younger age. Follow-up and further studies for higher age groups are required to accurately elucidate the MRI’s role in assessing cystinosis myopathy.

Pedal Vessel Calcification and Risk of Major Adverse Foot Events in the Diabetic Neuropathic, Nephropathic Foot.

We aimed to determine the relative risk of pedal vessel calcification (PVC) on major adverse foot events (MAFEs) and chronic kidney disease (CKD) stage in patients with diabetes mellitus (DM) and peripheral neuropathy (PN). We retrospectively reviewed electronic medical records of 152 patients with diagnoses of DM, PN, and CKD stages one to five who had at least one foot radiograph obtained. PVC was scored (from 0-4) based on foot anatomic location and radiology reported MAFEs, which includes foot fracture, Charcot neuroarthropathy, foot ulcer, osteomyelitis, or minor amputation. Risk ratios (RR) with 95% confidence intervals (95% CI) and Poisson regressions were performed assessing the risk of sustaining MAFEs with number of PVCs and stage of CKD. The risk of any MAFE increased as PVC score increased (RR = 1.23); the risk of any MAFE increased as CKD stage increased (RR = 1.35); and risk of any PVC increased as CKD stage increased (RR = 1.71). Pedal vessel calcification on a foot radiograph increases the risk of any MAFE and increases with progressive stage of CKD. Pedal vessel calcification may serve as a gateway to prompt investigation, treatment, or referral for at-risk diabetic neuropathic, nephropathic patients.

Plasma chitotriosidase enzyme activity as a novel therapeutic monitor for cysteamine treatment in nephropathic cystinosis: A retrospective validation study

BackgroundCystine-depleting therapy in nephropathic cystinosis is currently monitored via the white blood cell cystine assay, although its application and usefulness are limited by practical and technical issues. Therefore, alternative biomarkers that are widely available, more economical and less technically demanding, while reliably reflecting long-term adherence to cysteamine treatment, are desirable.Recently, we proposed chitotriosidase enzyme activity as a potential novel biomarker for the therapeutic monitoring of cysteamine treatment in cystinosis. In this study, we aimed to validate our previous findings and to confirm the value of chitotriosidase in the management of cystinosis therapy. Materials & methodsA retrospective study was conducted on 12 patients treated at the National Institutes of Health Clinical Center and followed up for at least 2 years. Plasma chitotriosidase enzyme activity was correlated with corresponding clinical and biochemical data. ResultsPlasma chitotriosidase enzyme activity significantly correlated with WBC cystine levels, cysteamine total daily dosage and a Composite compliance score. Moreover, plasma chitotriosidase was a significant independent predictor for WBC cystine levels, and cut-off values were established in both non-kidney transplanted and kidney transplanted cystinosis patients to distinguish patients with a good versus poor compliance with cysteamine treatment. Our observations are consistent with those of our previous study and validate our findings. ConclusionsChitotriosidase enzyme activity is a valid potential alternative biomarker for monitoring cysteamine treatment in nephropathic cystinosis patients. SynopsisChitotriosidase enzyme activity is a valid potential alternative biomarker for monitoring cysteamine treatment in nephropathic cystinosis patients.

Screening for Chronic Kidney Disease in Type 2 Diabetic Patients: Single Centre Study

Abstract Background Diabetes mellitus is the most common cause of chronic kidney disease in the world, leading to multiple complications including end-stage renal disease, cardiovascular disease and even death so, Screening is an important strategy to address the burden of CKD in diabetic population. International clinical guidelines recommend CKD screening for individuals with risk factors such as diabetes, using laboratory assessments of glomerular filtration rate (GFR) and urine albumin excretion. Objective This study describes the implementation and outcomes of screening programme for chronic kidney disease in type 2 diabetic patients to assess the burden of renal disease in diabetic population. Patients and Methods The present study included two hundred type 2 diabetic patients complicated with diabetic nephropathy. Fifty five percent of the studied patients were males. Age ranged from 42 to 82 years with mean ± SD of 60.09 ± 8.55 years. They were screened in Alagouza Hospital for CKD by using urinary ACR and average eGFR. Patients with CKD were further investigated for extrarenal diabetic complications as PVD, amputation and cardiovascular complications by using LL arterial duplex and echocardiography. Results As regard diabetic complications, nephropathy came in the 1st rank with 106 patients (53%) presented with either average eGFR<60 ml/min/1.73 m2(10.5%), ACR >30 mg albumin/gm creatinine (30%) or both(12.5%). That was followed by history of neuropathy which represented 44.5% of the studied patients. Retinopathy evidenced in fundus examination compromised about 34.516% out of our studied population. Patients with past history of stroke represented 17.5% of the studied population Peripheral neuropathy was more common in patients with nephropathy 69.7 % (n = 62) (4 patients with decline eGFR, 36 patients with albuminuria and 22 patients with both), compared to only 30.3 % (n = 27) non- nephropathic diabetic patients gave positive history of neuropathy. retinopathy was more common in patients with nephropathy (11 patients with declined GFR, 25 patients with albuminuria and 25 patients with albuminuria and declined GFR), versus only 8 patients in among the non-nephropathic diabetic patients had retinopathy evidenced in fundus examination. Stroke was more common among patients with nephropathy (4 patients with decline eGFR, 6 patients with albuminuria and 12 patients with albuminuria and declined eGFR), versus 13 patients with positive stroke history in non- nephropathic diabetic patients. Patients with nephropathy were further investigated for the presence of extra renal diabetic complications as PVD and cardiovascular complications. Arterial LL duplex revealed PVD in 32.1% (34 patients) with 3 patients underwent amputation. As regard cardiovascular complications, 17.9 % (19 patients) were found to have abnormal findings in echocardiography examination including heart failure and ischemic changes. Conclusion From our study, we showed the high burden of diabetic complications among the patients with type 2 diabetes especially renal diabetic complications. Therefore, screening of diabetic nephropathy in patients with type 2 diabetes mellitus can help in early treatment and avoid its more serious complications not only the progression to ESRD but also development of other extra-renal diabetic complications.

A literature review about cardiovascular risk in patients with kidney disease

More than 700 million individuals are thought to have chronic kidney disease (CKD) globally, and the incidence is continuing to rise as a result of an aging population and the spread of chronic illnesses like diabetes and hypertension. The most common cause of morbidity and death in nephropathy patients is cardiovascular disease. In clinical practice, managing nephropathy and cardiovascular risk in nephropathic patients is a significant problem. Each patient needs a thorough examination and specialized treatment. To lower the risk of cardiovascular events in nephropathy patients, cardiovascular risk factors must be prevented and promptly treated. To increase the quality of life and survival of nephropathic patients, it is crucial to recognize and treat cardiovascular problems.

Cognitive functions and behavioural profiles in children with cystinosis treated with cysteamine and correlation with treatment duration

BackgroundCystinosis is a rare autosomal recessive disease. Children with nephropathic cystinosis (NCTN) have evidence of intellectual dysfunction and behavioural abnormalities which are attributed to renal dysfunction, metabolic disarrangement, and gene mutation. This study aimed to characterize the cognitive functions and behavioural profiles in nephropathic cystinosis patients on cysteamine therapy, and determine its relation to cysteamine treatment duration. In this analytical cohort study, 20 children with nephropathic cystinosis aged 6 years or above were compared to 26 children with chronic kidney disease (CKD) matched in age, sex, and CKD stage. All patients were subjected to full clinical and psychometric assessment using the Child Behaviour Checklist (CBCL) and the Arabic language version of Stanford-Binet test (SB).ResultsThere was no significant difference between both groups regarding Stanford-Binet test (SB) and Child Behavioural Checklist (CBCL), apart from delinquent behaviour. Duration of cysteamine treatment was inversely correlated with short-term memory, thought, and sex problems.ConclusionsChildren with cystinosis have a wide range of neurocognitive and behavioural problems that still present after cysteamine treatment and may be related to impact of genetic mutation on brain structure and function. Longer duration of cysteamine treatment could have beneficial effects on some behavioural problems.

Extra Virgin Olive Oil and Cardiovascular Protection in Chronic Kidney Disease.

The high mortality related to chronic kidney disease (CKD) is not only due to the disease itself; in fact, CKD also represents an important risk factor for cardiovascular (CV) morbidity and mortality. Among the functional foods that seems to have cardioprotective action, extra virgin olive oil (EVOO) plays a pivotal health-promoting role. The aim of this study was to evaluate the possible cardioprotective effects of an EVOO containing a very high content (>900 ppm) of minor phenolic compounds (MPCs). The selected EVOO was analyzed by HPLC-DAD-MS to establish the MPC content. The Olea extract obtained from the selected EVOO was tested against the RAW 264.7 cell line in order to investigate its anti-inflammatory activity. We enrolled 40 CKD patients under conservative therapy for in vivo clinical testing. All CKD patients consumed 40 mL/day of raw EVOO for 9 weeks (T1). At baseline (T0) and at T1, we monitored the patients’ blood and urinary parameters. The patients’ body composition was assessed using bioelectrical impedance analysis and the carotid intima-media thickness (CIMT) using ultrasound imaging. At T1, we observed a decrease in inflammatory parameters, CIMT, and oxidative stress biomarkers. We also noticed improvements in lipid and purine metabolism, atherogenic indices, and body composition. Thus, this study highlighted the cardioprotective action of EVOO in nephropathic patients.

Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part I: From cardiovascular risk factors to the mechanisms of cardio-renal syndrome

Chronic kidney disease (CKD) and cardiovascular (CV) disease are highly prevalent conditions in the general population and are strictly connected to each other with a bidirectional interaction. In patients affected by CKD, the leading cause of morbidity and mortality is represented by CV disease, since CKD promotes the atherosclerotic process increasing inflammation, and modifying lipid and bone mineral metabolism. On the other side, a strict relationship exists between CKD and CV risk factors, which are prevalent in nephropathic patients and impose a stringent assessment of the risk of CV events in this population together with an optimized pharmacological approach, complicated by the coexistence of the two pathological conditions. The first part of this consensus document focuses on the mechanisms of cardio-renal damage and on the impact, as well as the management, of the main CV risk factors in the context of CKD.

Utility of SIFT-MS to evaluate volatile organic compounds in nephropathic patients’ breath

Several studies highlighted a correlation between exhaled air volatile organic compounds (VOCs) and some pathological conditions, such as chronic kidney disease (CKD), chronic liver disease, etc. In fact, in literature has been reported that CKD is characterized by an increased concentration of ammonia, trimethylamine (TMA) and isoprene compared to healthy subjects. Currently, there is not a validate and standardized method to detect VOCs. For this purpose, we examined the utility of selected ion flow tube-mass spectrometry (SIFT-MS) to measure VOCs in CKD patients and we evaluated the possible correlation between VOCs and the presence of CKD and its stage. We enrolled 68 CKD patients under conservative therapy and 54 healthy subjects. The analysis of the VOCs of the exhaled air of the enrolled subjects was performed by SIFT-MS. Among all the VOCs analyzed, the most relevant results by ROC curves were observed for TMA, acetone, ammonia and dimethyl sulfide. We found that a breath TMA concentration superior to 26 ppbv characterizes a 6.11 times greater risk of CKD, compared to subjects with lower levels. Moreover, we detected an increased concentration of acetone and ammonia in CKD patients compared to healthy subjects. We highlight the potential utility of SIFT-MS in CKD clinical management.Clinical trial registry: R.S. 15.19 of 6 February 2019.

MO181: Clinical Characteristics and Short-Term outcomes of Hemodialysis Patients with SARS-COV-2 Infection: The Experience of a Covid Nephrology Unit

BACKGROUND AND AIMSSARS-CoV-2 pandemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients, such as nephropathic patients, are still scarce. Patients with chronic kidney disease (CKD) and on haemodialysis (HD) are at risk of a more severe disease course and worst outcomes. Here, we aimed to describe the characteristics and outcomes of CKD and HD patients with SARS-CoV-2 infection, admitted to the Covid Nephrology Unit in the first three pandemic waves, analysing mortality rate and risk factors for mortality in this subgroup of patients.METHODA Covid Nephrology Unit was organized in March 2020 to manage the high number of CKD and HD patients with SARS-CoV-2 infection. Several ‘spoke’ units were also set to manage HD asymptomatic patients (Hi Hotel and ‘Villa Luce’ Dialysis Center) or with mild symptoms (‘Miulli Hospital’-Acquaviva delle Fonti and ‘Fallacara Hospital’—Triggiano). Clinical and laboratory data in several timepoints were collected using electronic medical records. Primary outcome was to assess the mortality rate. Moreover, we analysed the trend of inflammatory markers in the first 7 days after hospital admission between survivors and non-survivors; finally, risk factors for mortality were analysed by logistic regression.RESULTSFrom March 2020 to May 2021, a total of 221 patients were admitted to the Covid Nephrology Unit; among these, 112 patients on chronic haemodialysis, 21 with acute kidney injury (AKI), 58 with CKD, 24 kidney transplant recipients and 6 patients on peritoneal dialysis (PD). Median age was 71 years (IQR 62.5–80), while male gender predominated (61.5%). Main comorbidities were arterial hypertension (81%), diabetes mellitus (41.8%) and cardiovascular disease (CVD, 60.6%). At admission, 13.2% of patients required non-invasive ventilatory (NIV) support (CPAP, BiPAP) and about 60% presented interstitial pneumonia at CT scan. A total of 80 patients (36.1%) died during hospital stay with a medium length of stay of 15.8 days. In the first 7 days, 29 patients presented respiratory failure requiring transfer to ICU. Conversely, 100 patients were discharged at home, while 48 patients were transferred to the spoke units (39 patients at Miulli and Fallacara Hospitals, 9 patients at Hi Hotel). Compared to survivors, patients who died were older (median age 75.5 versus 66 years, P < .001), characterized by more comorbidities (diabetes mellitus 54.5% versus 35.2%, P = .01; CVD 81.1% versus 51.4%, P < .001; chronic obstructive pulmonary disease (COPD, 41.5% versus 19%, P = .01; peripheral vasculopathy 58.4% versus 34.2%, P = .01) and more severe respiratory compromission at hospital admission (patients in NIV, 22.6% versus 8.1%, P = .005). As shown in Table 1, in the first 7 days of hospital stay, a significant increase in WBC (8.29 versus 12.6 × 106P < .001) was described in the non-survivor group; similarly, inflammatory markers such as CRP and IL-6 did not improve in the non-survivors at day 7 (CRP 81.8 versus 85.7 mg/L, P = .62; IL-6 63.1 versus 79.4 pg/mL, P = .84), while they significantly improved in survivors (median CRP 42.5 versus 10.1 mg/L, P < .001; median IL-6 32.3 versus 13.7 pg/mL, P = .01). In a multivariate logistic regression model, age (OR 1.062, 95% CI 1.007–1.119, P = .025), history of CVD (OR 8.308, 95%CI 1.704–40.499, P = .009) and dyspnoea at hospital admission (OR 9.465, 95%CI 1.231–72.79, P = .031) were associated with risk of mortality in this population. CONCLUSIONTo our knowledge, this is the largest study analyzing characteristics and outcomes of CKD and hemodialysis patients to date. A wide heterogeneity of severity of disease has been documented in our cohort; we documented a higher mortality rate in this cohort of patients compared to general population. The presence of several comorbidities, a more severe disease at hospital admission and the persistence of elevated inflammatory markers during hospital stay are risk factors for mortality.

MO1057: Cost-Analysis of a Clinical Workflow for Diagnosis of Inherited Kidney Diseases

Abstract BACKGROUND AND AIMS In the last decade, the use of whole-exome sequencing techniques (WES) has provided many insights into inherited kidney diseases that are thought to represent at least 10%–15% of cases of end-stage CKD [1]. However, among others, cost concerns limit the widespread of genomics use in daily practice [1, 2]. Publicly funded genomic testing is restricted in most health care systems [2]. Consequently, the evaluation of cost-effectiveness is urgently required in order to establish genomic sequencing as a standard diagnostic test for nephropathic patients. The aim of this study was to perform a cost-analysis of genetic testing use in a diagnostic workflow. METHOD We recently set up a diagnostic workflow for the selection of patients that should undergo genetic testing in the suspicion of a genetic disease. This algorithm is applied by a network of nephrology centres on the regional territory. Selected patients are referred to a tertiary centre, Meyer University Hospital of Florence (Italy), for genetic diagnosis by WES. We enrolled paediatric and adult patients referred to the outpatient service based on the pre-specified clinical criteria. All the patients underwent genetic testing from 2018 to June 2021. We conducted a cost-analysis in two parts: (1) assessment of the cost-effectiveness cut-off; and (2) exploratory modeled cost-analysis using WES in different phases of the diagnostic trajectory. As a surrogate of the cost-effectiveness analysis, we calculated the cost-effectiveness cut-off, indicating the amount of expenses for diagnostic examinations at which WES sequencing would be cost-effective. For the exploratory cost-analysis, we defined two diagnostic trajectories: Model I, considering an ideal complete diagnostic pathway and late use of WES; and Model II, considering an early use of WES allowing to save a certain number of examinations. Genomic and non-genomic investigations were obtained from local practice, available clinical evidence and guidelines. We then calculated the cost per diagnosis according to each Model for different clinical categories and for the whole study population using the diagnostic rates of this study. We considered only direct medical costs, based on the regional health reimbursement system, which is comprehensive of materials and human resources. The prices are expressed in euros. The analysis was conducted from a regional healthcare system perspective. RESULTS The analysis included 402 patients. WES performed after the standard non-conclusive diagnostic work-up (at a mean cost of €2992/patient) resulted in cost-effectiveness at a cost of &amp;lt;€2004/patient in the study population. Looking at different clinical categories, WES was cost-effective at a cost ranging from €3336 to €770. Overall, the exploratory cost-analysis showed Model II as cost reducing in comparison to Model I. The mean cost per diagnosis in Model I with late use of WES was estimated at €7700. Early use of WES in Model II had an estimated cost per diagnosis of €6340, leading to a cost saving of €1360/patient tested. Regarding the single clinical categories, the highest cost saving per diagnosis was obtained in podocytopathies (Model I: €13.010 versus Model II: €7261). The early use of WES produced a slight increase in estimated costs per diagnosis for tubulopathies, as well as for ciliopathies, while for syndromic CKD and metabolic kidney disorders, the costs per diagnosis did not result in major changes. CONCLUSION Early use of WES in the diagnostic pathway of inherited diseases, guided by a framework of specific criteria, is feasible and has the potential to produce substantial cost savings in healthcare.

Link between gut microbiota dysbiosis and chronic kidney disease.

During chronic kidney disease (CKD), typical alterations in the gut microbiota are observed. The kidney no longer plays the role of the main excretory organ as this function is performed by the intestine. In CKD patients, an alteration of intestinal permeability and a degradation of the protective mucous layer are observed. These changes in the intestinal barrier allow the passage of bacterial material from the intestine to the bloodstream through the intestinal wall. This phenomenon contributes to the induction of the chronic inflammatory state, typical of CKD. In nephropathic patients, there is an increase in circulation of p-cresyl sulfate (p-CS), indoxyl sulphate (IS), indole-3 acetic acid (IAA) and trimethylamine-N-oxide (TMAO), all gut-derived uremic toxins. The changes in gut microbiota composition are related to CKD stage and this phenomenon is exacerbated in hemodialysis (HD) adult and pediatric patients. Interestingly, it is observed a positive shift in gut microbiota composition after renal transplantation and at the same time a reduction of circulating gut-derived uremic toxins. Either gut dysbiosis or uremic toxins accumulation contribute to the CKD onset and progression.

Analysis of tear film in cystinosis patients treated with topical viscous cysteamine hydrochloride (Cystadrops®)

PurposeThe aim of this study was to evaluate in vivo the tear film in infantile nephropathic cystinosis patients with corneal crystals treated with topical viscous cysteamine hydrochloride (Cystadrops®).MethodsTen eyes of five patients with nephropathic cystinosis aged from 10 to 35 years were included in this study. The patients were under treatment with viscous cysteamine hydrochloride formulation containing 3.8 mg/mL cysteamine (vCH 0.55%, equivalent to 0.55% CH; Cystadrops®; Recordati rare Diseases, Puteaux, France) to reduce corneal crystal density. Five age and sex matched individuals were randomly selected as control group. Tear osmolarity testing (TearLabTM) was performed to assess the in vivo osmolarity of patients under treatment and compared to control group values. Tear film break-up time (TBUT) and basic tear secretion (Schirmer test) were also assessed.ResultsMean tear osmolarity was 294.8 mOsms/L (±10.4), with a mean absolute difference of 1.85 mOsms/L (±2.13) between the eyes. There was no statistically significant difference between the osmolarity readings of cystinosis and the control group (294.8 ± 10.4 vs 299.4 ± 6.2mOsm/L, respectively; p = 0.39). The mean TBUT was 10.2 ± 0.83 s in the study group versus 10 ± 0.7 s in controls (p = 0.62). The mean Schirmer test score was 9.2 ± 0.83 mm in the patients versus 10.2 ± 0.83 mm in the controls (p = 0.14).ConclusionsThe TearLabTM osmolarity system test showed good reliability and precision in repeated measurements. This is the first report using the TearLab osmolarity system to assess tear film in patients with cystinosis treated with vCH 0.55%. TearLabTM examination showed that the use of vCH 0.55% drops does not determine alterations of the tear film quality.

Natural Bioactive Compounds in the Management of Oral Diseases in Nephropathic Patients.

Among the chronic non-communicable degenerative diseases (CDNCDs), chronic kidney disease (CKD) represents a global public health problem. Recent studies demonstrate a mutual cause–effect relationship between CKD and oral diseases, in which the presence of one induces the onset and faster progression of the other. In particular, the oral cavity alterations more frequent in CKD patients are: chronic periodontitis diseases, bone lesions, oral infections, and oral cancer lesions. Currently, a standardized therapy for the treatment of oral diseases is lacking. For this reason, natural bioactive compounds (NBCs), characterized by several health effects, such as antioxidant, antimicrobial, anti-inflammatory and anti-cancer actions, represent a new possible adjuvant therapy in the management of these pathological conditions. Among NBCs, polyphenols play a leading role due to positive modulation of oral microbiota, preventing and correcting oral dysbiosis. Moreover, these compounds exert anti-inflammatory effects, such as inhibiting the production of pro-inflammatory cytokines and the expression of cycloxigenase-2. In this light, the formulation of a new mouthwash/gel/gingival paste, with a high content of polyphenols in association with NBCs characterized by antimicrobial action, could represent a future therapy of oral disease in CKD patients.

Screening for chronic kidney disease in Egyptian type 2 diabetic patients

Background Screening is an important strategy to address the burden of chronic kidney disease (CKD) in diabetic population. International clinical guidelines recommend CKD screening for individuals with risk factors such as diabetes using laboratory assessments of glomerular filtration rate (GFR) and urine albumin excretion. To assess the implementation and outcomes of screening programs for CKD in type 2 diabetic patients. Patients and methods A cross-sectional study was conducted that included 200 adult type 2 diabetic patients in Alagouza Hospital. Patients on hemodialysis and those with type 1 diabetes mellitus were excluded. Patients were screened for CKD using urinary albumin/creatinine ratio and average estimated glomerular filtration rate. Patients with CKD were further investigated for extrarenal diabetic complications such as peripheral vascular disease and cardiovascular complications. Results Overall, 55% of the studied patients were males, with a mean age of 60.09±8.55 years. Among diabetic complications, nephropathy was the most common (53%), followed by history of neuropathy (44.5%), and retinopathy evidenced in fundus examination (34.516%). History of stroke presented in 17.5% of patients. Peripheral neuropathy, retinopathy, and stroke history were more common in nephropathic patients compared with patients without nephropathy (62/27, 61/8, and 22/13, respectively). Patients with evidenced nephropathy who were further investigated for extrarenal diabetic complications showed peripheral vascular disease in 32.1% (34 patients), with three patients undergoing amputation. Heart failure and ischemic changes were seen in 17.9% (19 patients). Conclusion Screening of diabetic nephropathy in patients with type 2 diabetes mellitus helps in early treatment and avoids its more serious complications such as progression to end-stage renal disease and other extrarenal diabetic complications.

Biophysical and Immunological Characterization of Carbamylated-DNA: Serum Autoantibodies of Diabetic Nephropathy Patients Exhibit Strong Binding with Carbamylated-DNA

Isocyanates (ICN) have drawn considerable attention in recent past as they can react with a variety of nucleophiles including DNA, proteins and cause damage(s). However, pathophysiological implications resulting from the occupational and accidental exposures of ICN are yet too elusive. It may be produced in high concentrations in the conditions of chronic renal failure and chronic inflammatory diseases (diabetes mellitus, rheumatoid arthritis, etc.). In this study, mammalian dsDNA was modified with ICN and characterized by UV, fluorescence, FT-IR and thermal melting methods. ICN mainly reacts with exocyclic nitrogen of DNA bases. Antibodies against carbamylated-DNA were raised in rabbits and characterized by direct binding and inhibition ELISA. The presence of anti-carbamylated-DNA autoantibodies in the sera of diabetic nephropathy patients was evaluated by ELISA. Carbamylated-DNA exhibited hyperchromicity at 260 nm and depicted increase in ethidium bromide-assisted fluorescence as compared to the native DNA. Furthermore, the appearance of prominent new peaks in FT-IR profile at different wave numbers suggested carbamoylation-induced changes in the vibration of sugar-phosphate backbone, base(s) etc. Carbamylated-DNA was highly immunogenic as compared to the native DNA. Experimental induction of antibodies against carbamylated-DNA and presence of autoantibodies against carbamylated-DNA in the sera of diabetic nephropathic patients point towards the significance of carbamylated-DNA in diabetic nephropathy.

Prevalence of sarcopenia and associated factors in patients in hemodialysis

Objective: To assess the prevalence of sarcopenia and associated factors in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). Methods: This cross-sectional study evaluated patients with CKD undergoing HD from January to October 2016 in two dialysis centers located in Recife, Pernambuco. For the diagnosis of sarcopenia, the criteria proposed by the 2019 European Consensus on Sarcopenia, which advocates low muscle strength as the main criterion, were considered. Demographic, clinical, anthropometric, and behavioral covariates were evaluated. Results: 108 patients were included, with a mean age of 51.4 ± 17.0 years and homogeneous distribution between the sexes.Sarcopenia was present in 38.9% of the population, of which 69% had severe sarcopenia. A higher prevalence of sarcopenia was observed among men (60% vs. 17%; p &lt; 0.001), in those without a partner (48.1% vs. 30.4%; p &lt; 0.045), in smokers (50% vs. 30%; p &lt; 0.034), with low weight (underweight 73.3%, eutrophic 33.9%, overweight 32.4%; p = 0.001) and those with normal albumin levels (47.5% vs. 28.6%; p = 0.045). Conclusion: Approximately one in three nephropathic patients on hemodialysis presented sarcopenia and, among these, most had the severe form of this condition.Uremic sarcopenia was more prevalent in males, in individuals without partners, underweight, in smokers, and among those with normal albumin levels.

Clinical and neurophysiological characterization of early neuromuscular involvement in children and adolescents with nephropathic cystinosis.

Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by kidney and extra-renal complications due to the accumulation of cystine crystals in various tissues and organs. Herein, we describe the early neuromuscular complications in a cohort of pediatric nephropathic cystinosis patients. We prospectively evaluated the clinical, biochemical, and neurophysiological data of 15 cystinosis patients. Neurophysiological evaluation was performed to confirm or exclude presence of neuropathy and/or myopathy. Patients' age ranged between 20 and 216months at time of examination. Nine patients were males. Three patients had early abnormal neurophysiological features consistent with neuromuscular involvement (clinically asymptomatic proximal myopathy with a patchy distribution in one patient and isolated asymptomatic sensory nerve conduction changes in two patients). A fourth patient had mixed abnormal motor and sensory axonal neuropathic changes associated with overt clinical features (predominantly motor symptoms). Patients with abnormal neuromuscular features were significantly older in age than the unaffected group (P = 0.005) and had a diagnosis of cystinosis with subsequent cysteamine therapy at a significantly older age than the unaffected group (P = 0.027 and 0.001, respectively). We expanded the recognized phenotypes of cystinosis neuromuscular complications with early proximal skeletal myopathy and symptomatic motor and sensory axonal neuropathy. Early asymptomatic neuromuscular complications could develop in pediatric patients and would require neurophysiological studies for early detection prior to development of overt clinical manifestations. Prompt diagnosis and timely initiation of cysteamine therapy with recommended dose can delay the development of neuromuscular complications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Impact of Physical Activity and Natural Bioactive Compounds on Endothelial Dysfunction in Chronic Kidney Disease.

Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.

Effect of Hydrolysable Tannins and Anthocyanins on Recurrent Urinary Tract Infections in Nephropathic Patients: Preliminary Data

Urinary tract infections (UTIs) are caused by uropathogenic microorganism colonization. UTIs often require an antibiotic therapy that can cause the selection of antibiotic-resistant bacterial strains. A natural bioactive compound may represent a valid therapeutic adjuvant approach, in combination with drug therapy. In this paper, we present a pilot study, based on the administration of an oral food supplement (OFS), containing chestnut tannins and anthocyanins, to nephropathic patients suffering from recurrent UTIs (16 treated patients with 1 cp/day and 10 untreated patients). We performed laboratory tests and quality of life and body composition assessments, at T0 (baseline) and T1 (after 6 weeks OFS assumption). The analysis of OFS was performed by HPLC-DAD-MS for its content in polyphenols and by in vitro tests for its antioxidative and anti-free radical activities. In each capsule, polyphenol content was 6.21 mg (4.57 mg hydrolysable tannins, 0.94 mg anthocyanosides, 0.51 mg proanthocyanidins, 0.18 mg quercetin derivatives). A significant reduction of erythrocyte sedimentation rate was observed only in male patients. Urinalysis showed a significant reduction of leukocytes in both genders, whereas urinary bacterial flora at T1 significantly decreased only in male subjects. Tannins seem to exert an antimicrobial action according to gender, useful to counteract the recurrence of UTIs.