Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria.

AIMS/HYPOTHESIS: Abnormal gut microbiota and blood metabolome profiles have been reported both in children and adults with uncomplicated type 1 diabetes as well as in adults with type 1 diabetes and advanced stages of diabetic nephropathy. In this study we aimed to investigate the gut microbiota and a panel of targeted plasma metabolites in individuals with type 1 diabetes of long duration without and with different levels of albuminuria. METHODS: In a cross-sectional study we included 161 individuals with type 1 diabetes and 50 healthy control individuals. Individuals with type 1 diabetes were categorised into three groups according to historically measured albuminuria: (1) normoalbuminuria (<3.39 mg/mmol); (2) microalbuminuria (3.39-33.79 mg/mmol); and (3) macroalbuminuria (≥33.90 mg/mmol). From faecal samples, the gut microbiota composition at genus level was characterised by 16S rRNA gene amplicon sequencing and in plasma a targeted profile of 31 metabolites was analysed with ultra HPLC coupled to MS/MS. RESULTS: Study participants were aged 60 ± 11 years (mean ± SD) and 42% were women. The individuals with type 1 diabetes had had diabetes for a mean of 42 ± 15 years and had an eGFR of 75 ± 25 ml min-1 (1.73 m)-2. Measures of the gut microbial beta diversity differed significantly between healthy controls and individuals with type 1 diabetes, either with micro- or macroalbuminuria. Taxonomic analyses showed that 79 of 324 genera differed in relative abundance between individuals with type 1 diabetes and healthy controls and ten genera differed significantly among the three albuminuria groups with type 1 diabetes. For the measured plasma metabolites, 11 of 31 metabolites differed significantly between individuals with type 1 diabetes and healthy controls. When individuals with type 1 diabetes were stratified by the level of albuminuria, individuals with macroalbuminuria had higher plasma concentrations of indoxyl sulphate and L-citrulline than those with normo- or microalbuminuria and higher plasma levels of homocitrulline and L-kynurenine compared with individuals with normoalbuminuria. Whereas plasma concentrations of tryptophan were lower in individuals with macroalbuminuria compared with those with normoalbuminuria. CONCLUSIONS/INTERPRETATION: We demonstrate that individuals with type 1 diabetes of long duration are characterised by aberrant profiles of gut microbiota and plasma metabolites. Moreover, individuals with type 1 diabetes with initial stages of diabetic nephropathy show different gut microbiota and plasma metabolite profiles depending on the level of albuminuria. Graphical abstract.

A Clinical Study of Prevalence of Microalbuminuria in Patients of Primary Hypertension and its Correlation with Left Ventricular Mass Index.

INTRODUCTION: Hypertension is one of the most challenging health problems in the world. Hypertension is closely related to kidney diseases. Microalbuminuria is a reflection of early kidney dysfunction and a marker of asymptomatic preclinical disease which precedes and predicts the occurrence of major morbid events. AIMS AND OBJECTIVES: To investigate the relationship between microalbuminuria and LVH in patients with primary hypertension. To establish microalbuminuria as an independent risk factor for increased Left Ventricular Mass Index in patients with Primary Hypertension. METHODS: This was a cross-sectional prevalence, analytical study conducted for a period of two years in a tertiary care teaching hospital in Western India. 126 patients diagnosed as primary hypertension, according to JNC 7 criteria were included in the study. Left ventricular Mass Index was measured using 2 D Echo Machine using the formula of Left ventricular mass. Multiple logistic regression was conducted to find out independent correlation of Left Ventricular Hypertrophy. RESULTS: Mean age was 64.32 years in patients without LVH while it was 63.85 years in patients with LVH. Serum creatinine, albumin-creatinine ration and Microalbuminuria were independently correlated with the Left Ventricular hyper trophy. Multiple logistic regression concluded that presence of microalbuminuria increases risk of LVH 2.04 times more as compared to absence of microalbuminuria. Serum creatinine level was higher in patients with LVH compare to patients without LVH. patients with Microalbuminuria were higher in LVH group compare to non LVH group and this difference was statistically significant. CONCLUSION: This study demonstrates that microalbuminuria has an independent correlation with Left Ventricular Mass Index and hence an independent risk factor for increased cardiovascular morbidity and mortality.

Mucormicosis renal grave en un paciente crítico / Isolated renal mucormycosis in a critically ill patient

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Helicobacter pylori infection associated with type 2 diabetic nephropathy in patients with dyspeptic symptoms.

AIMS: The aim of this conventional case-control study was to investigate the prevalence and relationship between Helicobacter pylori infection in type 2 diabetes mellitus (DM) and diabetic nephropathy (DN). METHODS: A total of 241 type 2 DM patients and 69 non-diabetic subjects with dyspeptic symptoms were enrolled in the study. Gastroduodenal lesions were observed by gastrointestinal endoscopy and the presence of H. pylori was identified by rapid urease test and serum IgG antibodies to H. pylori. According to the urinary albumin excretion rate (UAE), patients were classified into diabetes mellitus group (DM group, with UAE <30 mg/24h); diabetic nephropathy group 1 (DN group 1, with UAE 30 mg/24 h to <300 mg/24 h); and diabetic nephropathy group 2 (DN group 2 ≥ 300 mg/24 h). The 69 non-diabetic subjects were used as control group. The serum levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 were determined using ELISA. RESULTS: The prevalence of H. pylori infection in DN group 1 and DN group 2 was 45/72 (62.5%) and 34/53 (64.15%), respectively, which was significantly higher than in control [28/65 (43.1%)] and DM groups [42.9% (27/63)]. No significant differences of H. pylori prevalence were detected between DN groups as well as DM and control groups. Interestingly, in both DN groups, higher levels of IL-8, TNF-α and urinary albumin excretion rate were found in H. pylori positive subjects. CONCLUSIONS: Diabetic nephropathy patients are more susceptible to H. pylori infection. Our data support an association between H. pylori infection and diabetic nephropathy.

Helicobacter pylori eradication reduces microalbuminuria in type-2 diabetic patients: a prospective study.

AIM: To evaluate the effect of Helicobacter Pylori (H. pylori) eradication on microalbuminuria in type 2 diabetic patients. METHODS: Consecutive patients with dyspepsia, type 2 diabetes mellitus and microalbuminuria were recruited. Upper gastrointestinal endoscopy and rapid urease test (H. pylori fast) were performed for detecting H. pylori infection. Patients with H. pylori infection were given triple treatment. Urea breath tests were performed for all patients after eradication treatment. According to the eradication status, patients were divided into two groups, as H. pylori negative, group 1 (successful eradication group) and H. pylori positive, group 2 (unsuccessful eradication group). Twenty-four hour urine was also collected from all patients at baseline and after H. pylori eradication treatment. RESULTS: A total of 69 patients were included in the study. There were no significant differences between groups for anthropometric measurements and laboratory tests at baseline (p > 0.05). An expected significant difference was found for microlabuminuria and fasting glucose between the two groups. Microalbuminuria and fasting glucose levels were signicantly reduced in the H. pylori negative group compared with the H. pylori positive group after eradication treatment (p < 0.05). Although there was no significant decline in HbA1c levels in the H. pylori negative group, there were relatively lower HbA1c levels compared with baseline for both groups. The rate of attaining normoalbuminuria after eradication was significantly higher in group 1 compared to group 2 (p < 0.05). CONCLUSION: H. Pylori eradication was found to have a favorable effect on reducing microalbuminuria in diabetic patients.

Impact of cytotoxin-associated gene A of Helicobacter pylori strains on microalbuminuria in type 2 diabetes.

Cytotoxin-associated gene A (CagA) positive strains of H. pylori have a significant correlation with gastritis and peptic ulcer, and may induce persistent systemic inflammatory response, increase vascular damage, and compromise glycemic control in diabetic patients. To evaluate correlation between infection by cagA positive strains of H. pylori and occurrence of microalbuminuria and glycemic control in type 2 diabetic patients, we prospectively studied 98 dyspeptic type 2 diabetic patients as a study group and 102 dyspeptic non-diabetic subjects as a control group. Gastric biopsy specimens obtained with endoscopy were cultured to isolate H. pylori. All the isolated H. pylori strains from cultures were used for detection of cagA gene by polymerase chain reaction. There was no significant difference between study and control groups regarding infection with cagA positive strains of H. pylori ( P= 0.145). Furthermore, there was no significant differences between both groups concerning the incidence of microalbuminuria ( P= 0.145). On the other hand, there was an extremely statistically significant difference in the incidence of microalbuminuria and glycemic control in the diabetic patients between those infected with cagA positive strains of H. pylori and cag A negative starins (P= 0.000). We conclude that infection with cagA positive strains of H. pylori are strongly associated with the increased incidence of microalbuminuria and poor glycemic control in type 2 diabetic patients.

Does bacteriuria interfere with albuminuria measurements of patients with diabetes?

BACKGROUND: Urinary albumin is the main parameter employed to diagnose diabetic nephropathy (DN). The exclusion of bacteriuria has been recommended at the time of DN diagnosis. This approach has been debated and information on this suggestion in patients with diabetes is scarce. The present case-control study was conducted to investigate the interference of bacteriuria in the interpretation of urinary albumin measurements in random urine samples of diabetic patients. METHODS: Urinary albumin concentration (UAC) was measured in random urine samples twice in diabetic patients with and without bacteriuria (> or =10(5) colony-forming units/mL). Cases (n = 81) were defined as patients who had baseline UAC measurement in the presence of bacteriuria and had the second UAC measured in a sterile urine sample. Controls (n = 80) had the two UAC measured in sterile urine specimens. RESULTS: Baseline UAC was not different between case [15.4 (1.5-2148) mg/L] and control groups [14.2 (1.5-1292) mg/L; P = 0.24], nor was the proportion of patients with normo-, micro- and macroalbuminuria. In cases, UAC measurements in the presence of bacteriuria and in sterile urine specimens were not different [15.4 (1.5-2148) versus 13.7 (1.5-2968) mg/L; P = 0.14)], nor was the proportion of normo- (51.9% versus 61.5%), micro- (40.7% versus 32.1%) and macroalbuminuria (7.4% versus 6.4%; P = 0.46). In the control group, UAC values were also not different in the two urine samples: [14.2 (1.5-1292) versus 9.7 (1.5-1049) mg/L, P = 0.22]. CONCLUSIONS: The presence of bacteriuria does not interfere significantly with urinary albumin measurements and its exclusion is not necessary to diagnose DN.

Microalbuminuria and comparison of serologic testing for exposure to Borrelia burgdorferi in nonclinical Labrador and Golden Retrievers.

Canine Lyme disease is caused by the spirochete Borrelia burgdorferi after transmission by an Ixodes tick, typically resulting in joint pain, fever and lethargy. Lyme nephritis is a poorly characterized syndrome associated with severe glomerular and tubular renal injury and poor clinical outcome in young to middle-aged dogs positive for exposure to B. burgdorferi. The aims of this study were to identify associations between natural exposure to B. burgdorferi and the presence of microalbuminuria in nonclinical young Labrador and Golden Retrievers and to compare two commonly used serologic tests available to document B. burgdorferi exposure: the Western blot and the commercial point-of-care C6 peptide enzyme-linked immunosorbent assay (ELISA) tests. Microalbuminuria was assessed using a commercial point-of-care ELISA specific for canine albumin. Blood and urine samples from 268 asymptomatic Labrador and Golden Retrievers were included. Of these, 18.7% were positive for B. burgdorferi exposure according to the C6 ELISA; 21.2% were positive for natural exposure to B. burgdorferi and 11.5% for vaccinal antibodies according to the Western blot. The agreement rate was 93% between the two tests (kappa = 0.78, P < 0.0001) for natural exposure. Urine from 6.1% of the dogs was positive for microalbuminuria. There was no association between microalbuminuria and exposure to B. burgdorferi based on results of a Western blot (P = 0.57) or C6 ELISA (P = 0.53). Microalbuminuria is likely not a consequence of B. burgdorferi exposure in young nonclinical Labrador and Golden Retrievers.

Proteinuria is associated with persistence of antibody to streptococcal M protein in Aboriginal Australians.

Aboriginal communities in Northern Australia with high rates of group A streptococcal (GAS) skin infection in childhood also have high rates of renal failure in adult life. In a cross-sectional study of one such high risk community, albuminuria was used as a marker of renal disease. The prevalence of albuminuria increased from 0/52 in subjects aged 10-19 years to 10/29 (32.9%) in those aged 50 or more (P < 0.001). Antibodies to streptococcal M protein, markers of past GAS infection, were present in 48/52 (92%) at ages 10-19 years, 16/32 (50%) at ages 30-39, and 20/29 (69%) in those aged 50 or more. After allowing for the age-dependencies of albuminuria and of M protein antibodies (P < 0.001) albuminuria was significantly associated with M protein antibodies (P < 0.01). Thus, 72% of adults aged 30 or more with M protein antibodies also had albuminuria, compared with only 21% of those who were seronegative. More detailed modelling suggested that although most Aboriginal people in this community developed M protein antibodies following GAS infection in childhood, the development of proteinuria was associated with the persistence of such seropositivity into adult life. The models predicted that proteinuria developed at a mean age of 30 years in seropositive persons, at 45 years in seronegative persons who were overweight, and at 62 years in seronegative persons of normal weight. We demonstrated a clear association between evidence of childhood GAS infection and individual risk of proteinuria in adult life. This study provided a strong rationale for prevention of renal disease through the more effective control of GAS skin infections in childhood and through the prevention of obesity in adult life.

Nefropatía diabetica / Diabetic nephropathy

Enfermedad de Kimelstiel-Wilson, denominada así en homenaje a estos dos investigadores que en 1.936 describieron las lesiones histopatológicas que se presentan en esta afección. Glomeruloesclerosis intercapilar diabética y enfermedad renal diabética. Constituye una temible devastadora complicación de la diabetes mellitus, caracterizada por proteinuria y reducción de la función renal, contribuyendo con un elevado número de pacientes con insuficiencia renal crónica terminal, a los programas de terapia renal sustitutiva