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Background: In a context where the prevalence of Diabetes Mellitus and Hypertension has increased significantly in recent years, kidney diseases become important for the potential demand for specialized health care and resources required., Objective: To analyze the geographical distribution of Diabetic Nephropathy (DN) and Renal Insufficiency (RI) based on the medical consultations given in first-level units of IMSS during 2019, to identify the medical units with the highest burden of care., Material and Methods: Ecological-exploratory study in which indicators were estimated for every thousand persons in relation to medical consultations given by ND and RI according to service time, first-level medical unit (UMF) and representation to analyze the magnitude and geographic distribution at the national level., Results: 45% of medical consultations were by ND and 52.4% by RI. The highest burden per DN was registered in UMF No. 50 Cd. Juarez (Chihuahua) and No. 49 Gabino Barreda (Veracruz Sur), with 1.7 first-time medical consultations and 148.3 subsequent medical consultations per 1,000 persons, respectively. While in UMF No. 40 Manlio Fabio Altamirano and No. 25 Cotaxtla, in Veracruz Norte, the highest burden was for RI, with 4.9 first-time medical consultations and 134.2 subsequent medical consultations per 1000 persons, respectively., Conclusions: The results could contribute to strengthening of medical units where it is necessary and the efficient allocation of resources available to meet the demand for health services of ND and RI in IMSS., (© 2022 Revista Medica del Instituto Mexicano del Seguro Social.)

Background: Diabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide., Objective: To determine the association of PPARγ rs1801282 polymorphism in T2DM and DN in south Indian population., Methods: We have conducted a case-control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN=128; T2DM=148 and controls=148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models., Results: The genotyping of rs1801282 polymorphism showed significant (p-value<0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value>0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR=0.56, (95%CI [0.43-0.74]), p≤0.0001 of Asian and Caucasian populations., Conclusion: Overall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case-control studies on the PPARγ gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Diabetic nephropathy (DN) is one of the most frequent complications in patients with diabetes mellitus (DM) and its diagnosis is usually established on clinical grounds. However, kidney involvement in some diabetic patients can be due to other causes, and renal biopsy might be needed to exclude them. The aim of our study was to establish the clinical and analytical data that predict DN and no-diabetic renal disease (NDRD), and to develop a predictive model (score) to confirm or dismiss DN., Material and Methods: We conducted a transversal, observational and retrospective study, including renal biopsies performed in type2 DM patients, between 2000 and 2018., Results: Two hundred seven DM patients were included in our study. The mean age was 64.5±10.6 years and 74% were male. DN was found in 126 (61%) of the biopsies and NDRD in 81 (39%). Diabetic retinopathy was presented in 58% of DN patients, but only in 6% of NDRD patients (P<.001). Patients with NDRD were diagnosed of primary glomerulopathies (52%), nephroangiosclerosis (16%), inmunoallergic interstitial nephritis (15%) and vasculitis (8.5%). In the multivariate analysis, retinopathy (OR26.7; 95%CI: 6.8-104.5), chronic ischaemia of lower limbs (OR4,37; 95%CI: 1.33-14.3), insulin therapy (OR3.05; 95%CI: 1.13-8.25), time course of DM ≥10years (OR2.71; 95%CI: 1.1-6.62) and nephrotic range proteinuria (OR2.91; 95%CI: 1.2-7.1) were independent predictors for DN. Microhaematuria defined as ≥10 red blood cells per high-power field (OR0.032; 95%CI: 0.01-0.11) and overweight (OR0.21; 95%CI: 0.08-0.5) were independent predictors of NDRD. According to the predictive model based on the multivariate analysis, all patients with a score >3 had DN and 94% of cases with a score ≤1 had NDRD (score ranked from -6 to 8points)., Conclusions: NDRD is common in DM patients (39%), being primary glomerulonephritis the most frequent ethology. The absence of retinopathy and the presence of microhematuria are highly suggestive of NDRD. The use of our predictive model could facilitate the indication of performing a renal biopsy in DM patients., (Copyright © 2019 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Current diagnostic methods are not very sensitive to detect the initial stages diabetic nephropathy of type 2. In this work, a review of metabolomic approximation studies for the identification of biomarkers of this disease with potential to differentiate between early stages, evaluate and direct treatment and help slow kidney damage. Using public (Pubmed and Google Scholar) and private (Scopus and Web of Knowledge) databases, a systematic search of the information published related to metabolomics of diabetic nephropathy in different biospecimens (urine, serum, plasma and blood) was made. Later, the MetaboAnalyst 4.0 software was used to identify the metabolic pathways associated with these metabolites. Groups of potential metabolites were identified for monitoring diabetic nephropathy with the available literature data. In the urine, oxide-3-hydroxyisovalerate, TMAO, aconite and citrate and hydroxypropionate derivatives are highlighted; meanwhile, in the serum: citrate, creatinine, arginine and its derivatives; and in the plasma: amino acids such as histidine, methionine and arginine has a potential contribution. Using MetaboAnalyst 4.0 the metabolic pathways related to these metabolites were related. The search for biomarkers to measure the progression of diabetic nephropathy, together with analytical strategies for their detection and quantification, are the starting point for designing new methods of clinical chemistry analysis. The association between the metabolic pathway dysfunction could be useful for the overall assessment of the treatment and clinical follow-up of this disease., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Increasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (rs861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population., Materials and Methods: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism., Results and Conclusion: Polymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14-8.40 and OR 3.29 95% CI 1.23-8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up., Materials and Methods: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis., Results: Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality., Conclusions: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m 2 . In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: The main objective of this study was to assess the percentage of co-morbid nephropathy in type 2 diabetes patients using the CKD-EPI equation and to compare the clinical characteristics and treatments of patients with type 2 diabetes with nephropathy with those of patients without nephropathy PATIENTS AND METHODS: This was a cross-sectional analysis of the demographic and clinical data registered in the IDIBAPS Biobank database. Patients were considered to have nephropathy if the diagnosis was reported in their clinical history, albuminuria (>30 mg/g) was indicated as present in the last urine test available, or an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m 2 was calculated using the CKD-EPI equation., Results: Clinical data were obtained from 1,397 patients with a diagnosis of type 2 diabetes. The percentage of patients with nephropathy was 29.3% (N= 369) (95% confidence interval, 26.8% to 31.9%); however, only 109 (7.8%) patients had a nephropathy diagnosis reported in their clinical history. Compared with patients without nephropathy, patients with nephropathy have a higher mean age, higher frequency of diabetes complications and received insulin more frequently., Conclusion: Our results show that the percentage of type 2 diabetes patients with nephropathy was high and that this comorbidity was associated with a significantly higher frequency of diabetes macro- and microvascular complications (compared to diabetes patients without DKD)., (Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Simultaneous pancreas-kidney transplantation (SPKT) constitutes the therapy of choice for diabetes type1 or type2 associated with end-stage renal disease, because is the only proven method to restore normo-glicemic control in the diabetic patient., Methods: Retrospective and descriptive study of a series of 175 patients who underwent SPKT from March 1995 to April 2016. We analyze donor and recipient characteristics, perioperative variables and immunosuppression, post-transplant morbi-mortality, patient and graft survival, and risk factors related with patient and graft survival., Results: Median age of the donors was 28years and mean age of recipients was 38.8±7.3years, being 103 males and 72 females. Enteric drainage of the exocrine pancreas was performed in 113 patients and bladder drainage in 62. Regarding post-transplant complications, the overall rate of infections was 70.3%; graft pancreatitis 26.3%; intraabdominal bleeding 17.7%; graft thrombosis 12.6%; and overall pancreas graft rejection 10.9%. The causes of mortality were mainly cardiovascular and infectious complications. Patient survival at 1, 3 and 5-year were 95.4%, 93% and 92.4%, respectively, and pancreas graft survival at 1, 3 and 5-year were 81.6%, 77.9% y 72.3%, respectively., Conclusions: In our 20-year experience of simultaneous pancreas-kidney transplantation, the morbidity rate, and 5-year patient and pancreas graft survivals were similar to those previously reported from the international pancreas transplant registries., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

Chronic kidney disease is a common complication of diabetes. Its importance lies in its high prevalence and future projection. It is associated with high health costs and global cardiovascular deterioration as well. The development of this disease pathophysiology is being studied and it is known that a series of complex molecular pathways determining a microvascular disease are involved. This review addresses the known pathways in the development of diabetic nephropathy aiming to improve the understanding of potential therapeutic targets that could be developed in the future.

Objectives: Due to the shortage of living kidney donors and the current diabetes mellitus (DM) pandemic, studying the association of solitary kidney (SK) with DM is of paramount importance. Our aim was to assess the significance of the association between SK and DM., Materials and Methods: Eighty-four patients with SK and DM (group A), with a mean age of 62.46±12.72 years, of whom 36 were males and 48 were females, were enrolled in the study. The control group (group B) comprised 84 SK patients without DM of similar age and duration of existence of a SK. Mean age: 61.58±8.22 years, 23 males and 61 females. Serum creatinine, GFR (CKD-EPI), glycaemia, cholesterol, triglycerides, uric acid, proteinuria/24h, systolic blood pressure (SBP), diastolic blood pressure (DBP) and BMI were assessed., Results: The group of patients with SK and DM (group A) had a higher BMI (p=0.0007), higher metabolic abnormalities (higher glycaemia [p<0.001], triglycerides [p=0.0004], uric acid [p=0.019] and proteinuria/24h [p=0.006]). The study group also had a higher prevalence of hypertension (p=0.003) and coronary artery disease (p=0.031)., Conclusions: We found a higher value of proteinuria in the study group, significant metabolic abnormalities, as well as a higher prevalence of hypertension and coronary artery disease. However, no differences with respect to GFR were found, which could have significant implications for transplantation., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Albuminuria was widely considered as the first clinical sign of diabetic kidney disease (DKD), which is why it has traditionally been used as a screening test for DKD. However, increasing evidence has shown that a significant number of type 2 diabetes mellitus (DM) patients have a decreased glomerular filtration rate (GFR) without significant albuminuria, known as non-albuminuric DKD (NA-DKD). The aim of this study was to determine the prevalence and the demographic and clinical characteristics of patients with NA-DKD., Methods: This was a 1-year retrospective study that included 146 type 2 diabetic patients with GFR<75mL/min followed-up in a diabetes outpatient department. Patients were divided into two groups according to their ACR status - NA-DKD and albuminuric DKD (A-DKD)., Results: Of the 146 patients included in the study, 53.4% had A-DKD and 46.6% had NA-DKD. According to the multivariable analysis performed, patients with NA-DKD tended to be older (p=0.021), female (p=0.045) and with a lower GFR (p=0.004) than A-DKD patients. There was no difference between the groups in terms of body mass index, metabolic control of DM, duration of DM diagnosis and prevalence of metabolic syndrome., Conclusions: The majority of patients with DKD had albuminuria, but a significant proportion had a non-albuminuric phenotype (46.6% in this population). These patients exhibit distinct clinical features that could have screening, therapeutic and prognosis implications., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Diabetic renal lesions can only be diagnosed by kidney biopsy. These biopsies have a high prevalence of non-diabetic lesions. The aims of the study were to determine the predictability of non-diabetic nephropathy (NDN) in diabetics and study differences in survival and renal prognosis. In addition, we evaluated histological lesions and the effect of proteinuria on survival and renal prognosis in patients with diabetic nephropathy (DN)., Material and Methods: A descriptive, retrospective study of kidney biopsies of diabetics between 1990 and 2013 in our centre., Results: 110 patients were included in the study: 87 men (79%), mean age 62 years (50-74), mean serum creatinine 2.6mg/dl (0.9-4.3) and proteinuria 3.5g/24hours (0.5-6.5). 61.8% showed NDN, 34.5% showed DN and 3,6% showed DN+NDN. The most common NDN was IgA nephropathy (13,2%). In the multivariate analysis, creatinine (OR: 1.48, 1.011-2.172, p=0.044), proteinuria/24hours (OR: 0.813, 0.679-0.974, p=0.025), duration of diabetes (OR: 0.992, 0.987-0.998, p=0.004), age (OR: 1.068, 95% CI: 1.010-1.129, p=0.022), and diabetic retinopathy (OR: 0.23, 0.066-0.808, p=0.022) were independently associated with NDN. We did not find any differences in survival or renal prognosis. Concerning patients with DN, increased nodular mesangial expansion (p=0.02) and worse renal prognosis (p=0.004) were observed in nephrotic proteinuria as compared to non-nephrotic proteinuria. We did not find differences in patient survival., Conclusions: The most common cause of NDN was IgA nephropathy. Higher creatinine levels, shorter duration of diabetes, absence of diabetic retinopathy, lower proteinuria, and older age were risk factors for NDN. Patients with DN and nephrotic-range proteinuria had worse renal prognosis., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Residual renal function (RRF) contributes to the quality of life of patients on dialysis. The preservation of RRF is associated with higher patient survival in peritoneal dialysis (PD), and is now accepted that RRF and peritoneal clearance are not of equal value in patient survival. The aim of this study is to know the factors related to RRF loss in prevalent patients in continuous ambulatory peritoneal dialysis (CAPD)., Methods: This is an analysis of secondary outcomes. Forty-three adult patients with type 2 diabetes were included. They had RRF preserved. Clinical and laboratory assessments were done in each visit during a year., Results: The male gender (p = 0.042), systolic (p = 0.009) and diastolic (p = 0.006) blood pressure (BP), hemoglobin (p = 0.008), peritoneal creatinine clearance (p = 0.014), peritoneal ultrafiltration (p = 0.017) and levels of tumor necrosis factor-alpha (TNF-alpha) in plasma (p = 0.022) and dialysate (p = 0.008) were related with RRF loss., Conclusions: It is important to understand the factors associated with RRF loss in our patients to prevent the gradual loss and its implications on the mortality and quality of life.

The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives., (Copyright © 2015. Published by Elsevier España, S.L.U.)

The diabetic kidney presents excess expression and activity of the SGLT2 transporter of the proximal tubule. This situation increases the renal reabsorption of Na and glucose and reduces their distal supply. In addition to the metabolic effects on the internal environment of this excess reabsorbed glucose, the renal tubule is subjected to glycosylated stress capable of locally activating both apoptosis and inflammasome. The result is a progressive loss of nephron units, activation of transition of mesangial epithelium and collagen deposition. Activation of insulin signalling by the MAP kinase pathway and resistance to the metabolic effects of insulin take place. This is simultaneously combined with afferent vasodilation due to hyperglycaemia, tubuloglomerular feedback inhibition due to reduced distal fluid supply, podocyte dedifferentiation and reduction in their number, the latter effects being due to insulin resistance. The result is self-feeding renal damage, with intraglomerular hyper-pressure, podocyte dedifferentiation, tubular apoptosis, and local and distant activation of inflammasome. All these effects are susceptible to be totally or partially corrected by inhibiting glucose transport via the SGLT transporters., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Introduction: Certain polymorphisms in the non-muscle myosin IIA (MYH9) and apolipoprotein L1 (APOL1) genes have been associated to chronic kidney disease (CKD) in different populations. This study examined the association between the MHY9 rs2032487 and APOL1 rs73885319 polymorphisms and advanced CKD related to type 2 diabetes mellitus (T2DM) in a population of Gran Canaria (Canary Islands, Spain)., Patients and Methods: Polymorphisms were genotyped in 152 patients with advanced CKD (estimated glomerular filtration rate [eGFR]<30mL/min/1.73 m 2 ) secondary to T2DM, 110 patients with T2DM onset ≥ 20 years before without advanced CKD (eGFR ≥ 45mL/min/1.73 m 2 and no proteinuria), and 292 healthy blood donors over 50 years of age without CKD or diabetes., Results: The frequency of the risk allele for rs2032487 was 10.7% in patients with diabetes and advanced CKD, 7.1% in those with diabetes but without advanced CKD, and 6.1% in healthy subjects, with significant differences between the first and third groups (P=.015). Among subjects with advanced CKD, 78.5% were homozygous for the protective allele, as compared to 87.9% in the other two groups (P=.015 and P=.016 respectively). The frequency of the risk allele for the rs73885319 polymorphism did not exceed 0.5% in any of the three groups., Conclusions: These data suggest that polymorphism rs2032487 is associated to advanced CKD related to T2DM in the population of Gran Canaria., (Copyright © 2019 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1)., Methods: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15±32.45ml/min) with a mean age 58.13±12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year., Results: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r=0.714, p=0.0004) and with the tubular injury marker KIM-1 (r=0.758, p=0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r=0.53, p<0.01), KIM-1 (r=0.49, p<0.05) and s-Klotho (r=0.52, p<0.01)., Conclusion: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1., (Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objective: The aim of this study was: to estimate the prevalence of chronic renal insufficiency (CRI) in diabetic type 2 (DM2) patients treated in Primary Care based on the estimated glomerular filtration rate (GFe); to determine associated factors with CRI, and to evaluate the relationship of GF rate and risk of cardiovascular disease., Patients and Methods: This was a descriptive cross-sectional study. We included 500 medical histories randomly selected in a total of 2,950 DM2 patients. We registered sociodemographic data, comorbidities, cardiovascular risk factors and laboratory data. CRI definition was based on GFe rate and classified according to the K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease., Results: The prevalence of CRI was 23.2%. There were 51.6% females and the mean age was 66.2 years; 70,4% had hypertension and 67% dyslipidemia. The presence of CRI was related with older age, females, smoking habit, plasma creatinine value, microalbuminuria, and history of hypertension, dyslipidemia and cardiovascular disease. After analysing the data according to the category of GF rate, only the significant relationship with smoking habit disappeared. Multivariate statistic analysis supports a relation with older age, female gender, dyslipidemia and heart disease., Conclusions: We confirm a high prevalence of CRI in DM2 patients and their relationship with the presence of cardiovascular disease., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

In this paper we analyse the discrepancies that exist in the widespread prescription of metformin in patients with type 2 diabetes and the lack of guidelines concerning its prescription in the different stages of renal failure. This cross-sectional study includes 304 patients with type 2 diabetes treated with oral antidiabetic drugs (ADOs) and a glomerular filtration rate (estimated GFR) &lt;60ml/min/1.73m2. Patients were attended in consecutive visits to primary health centres or in hospital departments of endocrinology or nephrology during 2010. We studied the frequency of metformin and other ADO prescriptions according to renal function and the department in which the patient was treated. The ADO most frequently prescribed was metformin (54.9%), followed by repaglinide (47.7%), DPP4 inhibitors (28.6%), and sulfonylureas (18.4%). However, in nephrology departments, repaglinide was more frequently prescribed than metformin (P&lt;.001), whereas in primary health centres, the prescription of DPP4 inhibitors increased. In patients with an estimated GFR of 15-29ml/min/1.73m2, metformin (13.3%) and sulfonylureas were the least prescribed, whereas metformin was much more frequently prescribed (70.0%) when estimated GFR was 45-59ml/min/1.73m2 (P&lt;.001). In contrast, patients with an estimated GFR of 15-29ml/min/1.73m2 were mainly prescribed repaglinide (76.7%), as opposed to patients with an estimated GFR of 45-59ml/min/1.73m2 (38.9%) (P&lt;.001). Substantial evidence suggests that the recommendations for the use of ADO should be modified. This would lead to safely prescribing ADO in patients with an estimated GFR&lt;60ml/min/1.73m2, and more importantly in medical practice, according to the law.

Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone of B cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electrón microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. The patient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuria persisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. The patient received hemodialysis for six months and continued with methylprednisolone.

Diabetic neuropathy is the third most common complication of diabetes mellitus. When this neuropathy is accompanied by pain, it requires a specific treatment. In the elderly patient, the pain has an enormous impact on quality of life, as it is associated with anxiety, depression and sleep disorders, leading to a direct impact on the functionality of the patient. Likewise, there are a number of changes at the central and peripheral nervous system, which contribute to the chronicity of painful processes, and eventually also affect and impact on the quality of life of elderly patients. It is fundamental before initiating treatment, to know of all aspects related to drug pharmacokinetics and pharmacodynamics, especially those related to aging, because this will allow you to select the best drug for each patient. This article aims to review the pathophysiological concepts related to diabetic neuropathy in the elderly and the best treatment options.

Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

Diabetic nephropathy is the most common cause of endstage renal disease. Approaches targeting angiotensin II significantly delay its progression. However, many patients still need renal replacement therapy. High throughput techniques such as unbiased gene expression profiling and proteomics may identify new therapeutic targets. Cell death is thought to contribute to progressive renal cell depletion in chronic nephropathies. A European collaborative effort recently applied renal biopsy transcriptomics to identify novel mediators of renal cell death in diabetic nephropathy. Twenty-five percent of cell death regulatory genes were upor downregulated in diabetic kidneys. TNF-related apoptosisinducing ligand (TRAIL) and osteoprotegerin had the highest level of expression. In diabetic nephropathy, tubular cells and podocytes express TRAIL. Inflammatory cytokines, including MIF via CD74, upregulate TRAIL. A high glucose environment sensitized renal cells to the lethal effect of TRAIL, while osteoprotegerin is protective. These results suggest that, in addition to glucose levels, inflammation and TRAIL are therapeutic targets in diabetic nephropathy.

Objective: to measure the baseline urinary excretion of nitric oxide metabolites and their changes after an oral acute protein load (APL) and after a short-course with a low-dose captopril treatment in children with I-II stages of diabetic nephropathy., Methods: eleven children with early diagnosis of insulin dependent diabetes mellitus and with poor metabolic control were studied. Urinary excretion of nitric oxide metabolites (UENOm) and renal functional reserve with iothalamate clearance were measured, before and after an APL both in baseline form and after 15 days with captopril treatment., Results: In pre-treatment period the UENOm was 1113 +/- 797 and after APL was 1800.10 +/- 1329.07 nmol\mL\minute (ns). Glomerular filtration rate (GFR) was 159.5 +/- 42.1 and post-APL was 149.3 +/- 41.2 mL/minute 1.73 m2 (ns). Post-captopril treatment, UENOm 2316.30 +/- 1392 and after APL was 1514.49 +/- 685 nmol\mL\minute (ns). GFR pre-APL was 119.6 +/- 28.8 mL/minute 1.73 m2, p<0.03 versus GFR baseline precaptopril) and post-APL was 135.0 +/- 15.0 ml/minute 1.73 m2, p<0.05 versus GFR baseline post-captopril). The renal plasmatic flow and the filtration fraction did not have significative changes., Conclusions: the renal functional reserve was restored with captopril despite the poor metabolic control. It is difficult to identify if the basal UENOm were elevated because, the normal values were unknown in association with the poor metabolic control. And it's interesting that the captopril decreases the GRF and the UENOm rises without correlation with or without renal functional reserve and changes in UENOm.

Background: Despite a better management of the variables that influence the development of diabetic nephropathy there is a progressive increase in the prevalence of terminal renal failure among diabetics, whose cause is not clear., Aim: To study in a group of patients in hemodialysis, the quality of diabetes control previous to the entry to dialysis, their physical condition and their evolution., Material and Methods: Diabetic patients with at least three months of hemodialysis answered a questionnaire about diabetes control quality previous to dialysis and had physical and laboratory assessment. They were followed for at least four years thereafter., Results: Fifty seven patients aged 62+/-11 years were studied. Eighty four percent had some degree of disability. Eighty seven percent had high blood pressure and 73% had to enter dialysis as an emergency. Mean glycosilated hemoglobin was 7.7% and 58% had a dialysis dose with a Kt/Vofless than 1.2. Fifty eight percent died during follow up. No relationship between mortality and age, blood pressure, glycosilated hemoglobin of Kt/V, was observed., Conclusions: There is an inadequate management of blood glucose and blood pressure of diabetic patients before entry to dialysis. They are referred inverted exclamation markate to the nephrologist, the dialysis dose is insufficient and they have a high mortality.

Objective: to evaluate a personalized diet customize for present comorbidity, on metabolic control indicators and renal function., Methods: a non-randomized clinical trial was conducted during a three-month period in a group of patients with microalbuminuria and in a group with macroalbuminuria. The patients received personalized dietary counseling customize to their comorbidity (obesity, hypertension, and dislypidemia). The effect of the diet was measured through metabolic control variables: body mass index (BMI), waist circumference, fasting glucose levels, glycated hemoglobin (HbA(1))c and lipids profile; the renal function variables were: glomerular filtration rate (GFR) and urine albumin excretion (UAE). Statistical analysis was done with t-paired test., Results: thirty-nine patients were included (21 women and 18 men). After the intervention, the weight and waist circumference had significantly decreased (p = 0.01); the fasting glucose levels and HbA(1)c were significantly lower (p = 0.001). The HDL-cholesterol increased significantly (p = 0.009); UAE decreased significantly in patients with micro and macroalbuminuria; 123.0 +/- 73.4 to 105.3 +/- 61.3 mg/24-h; p = 0.040 and 1482.7 +/- 1200.6 to 1093.5 +/- 601.8 mg/24-h; p = 0.02. The GFR increased in both groups: 68.9 +/- 35.4 to 74.7 +/- 41.6 mL/min, p = 0.04; and 62.2 +/- 26.6 to 68.5 +/- 25.3 mL/min, p = 0.02., Conclusions: the dietary intervention improved the metabolic control and renal function in type 2 diabetes patients with comorbidity.

Objectives: Evaluate the effect of spironolactone (SPL) on the loss of podocytes during the progression of experimental diabetic nephropathy (DN)., Materials and Methods: A group of male Holtzman rats randomly received streptozotocin (diabetic group) or a buffer citrate (control group). Diabetic rats were treated with SPL (50 mg/kg/day). The glomerular area and the cellularity were evaluated by histomorphometric methods. The injury and loss of podocytes was assessed by desmin expression and Wt-1, respectively. The gene expression of TGF-β1 was assessed by RT-PCR., Results: Glucose levels, the glomerular area, the mesangial expansion and collagen content increased significantly in diabetic rats. The administration of SPL prevented these changes without changing glucose levels. Immunostain for Wt-1 decreased significantly while immunostain for desmin increased dramatically in diabetic rats. Treatment with SPL prevented the increase of desmin expression and the loss of Wt-1 expression. Furthermore, the administration of SPL prevented the increase of TGF-β1 mRNA expression in diabetic rats., Conclusions: Treatment with SPL, through independent glucose effects, reduces the loss of podocytes and the progression of DN morphological changes. These results suggest that these effects are mediated, at least in part, by the inhibition of TGF-β1 mRNA expression.

Background: Type 2 diabetes mellitus is the main cause of chronic kidney disease in developed countries., Aim: To study the prevalence of chronic kidney disease among adults with diabetes mellitus attended at a public primary health care clinic in southern Chile., Material and Methods: One hundred patients with type 2 diabetes mellitus, aged more than 15 years participated in this cross sectional study. Chronic kidney disease was defined as the presence of a urine albumin/creatinine ratio over 30 mg/g or an estimated glomerular filtration rate of less than 60 mL/min/1,73 m², detected in at least two opportunities, separated at least by three months., Results: Thirty four percent of participants had chronic kidney disease (17% stage 1 or 2 and 17% stage 3). Thirty percent of participants had an abnormal urinary albumin/creatinine ratio. Halfof the patients with an estimated glomerular filtration rate below 60 mL/min/1,73 m², had a normal urinary albumin/creatinine ratio., Conclusions: The rates of chronic kidney disease in this group of diabetic patients are very similar to those reported elsewhere.

Background and Objective: Diabetic retinopathy is a microvascular complication of diabetes mellitus whose prevalence is closely related to the presence of nephropathy and hypertension. The aim was to study clinical and pharmacological factors that are associated with an increased need for laser photocoagulation in patients with diabetic nephropathy and retinopathy., Patients and Methods: Cross sectional study of 63 patients followed in the Diabetic Nephropathy consultation. Patients were divided into 2 groups according to whether or not previously have received photocoagulation. In each subgroup were studied demographic variables, anthropometric, laboratory, cardiovascular risk factors and treatment received by each patient for the control of hypertension, diabetes and others diseases., Results: We observed that the group had received photocoagulation had more years of diabetes evolution, more history of cardiovascular disease and a lower creatinine clearance. Similarly, the percentage of patients treated with carvedilol was significantly higher in the subgroup who had not received photocoagulation while the percentage of patients treated with beta-blockers was significantly higher in the subgroup that received photocoagulation; no significant differences was observed in the degree of control blood pressure., Conclusions: Clinical and pharmacological factors related to the requirements of laser photocoagulation were years of diabetes evolution, history of cardiovascular disease, the stage of kidney disease and the treatment with beta-blockers., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Background: The presence of cardiac autonomic neuropathy (CAN) in patients with diabetes mellitus (DM) is associated with increased mortality and chronic microvascular complications of diabetes., Objective: To investigate a possible association between specific findings of CAN during exercise testing (ET) and nephropathy and retinopathy in patients with type 1 DM., Methods: We conducted a cross-sectional study of 84 patients with type 1 DM. All patients underwent clinical laboratory evaluation and performed ET, and those who presented findings suggesting myocardial ischemia were excluded from data analysis (n = 3). The assessment of microvascular complications (retinopathy and nephropathy) was performed in the sample., Results: Patients with nephropathy and those with retinopathy achieved a lower heart rate (HR) at peak exercise (HR max) and smaller increase in HR in relation to rest (Peak ΔHR) compared with those without these complications. These patients also had a smaller reduction in HR in the second and 4(th) minutes after the end of the test (ΔHR recovery 2 and 4 minutes). After performing a multivariate analysis with control for possible confounding factors, the ΔHR recovery in two and four minutes, maximum HR and Peak ΔHR remained significantly associated with retinopathy; and ΔHR recovery in the second and 4(th) minutes remained associated with the presence of nephropathy., Conclusion: The ET can be considered an additional tool for early detection of CAN and to identify patients at increased risk for microvascular complications of diabetes.

Objective: To evaluate the level of compliance with the 2002 consensus document (Spanish Society of Nephrology) on guidelines for the detection, prevention and treatment of diabetic nephropathy in Catalonia., Subjects and Methods: Multicenter (23 hospitals), observational, cross-sectional, descriptive study conducted in 413 diabetic patients (61.7% men, 38.3% women) with a median age of 66.2 +/-11.5 years (26-93 years). The ANOVA test (post-hoc analysis; p value< 0.05) was used to study the relationships between the stages of diabetic nephropathyand different variables., Results: 90.3% of the patients had type 2 DM. The following anthropometric parameters were observed: BMI 29.8 +/- 5 kg/m2 (BMI > 30 kg/m2: 48.7%) and waist circumference 104.1 +/- 14 cm (48.6% men > 102 cm and 78.9% women > 88 cm). Serum creatinine 1.9 +/- 1.3 mg/dl and simplified MDRD equation 45.3 +/- 25.0 ml/min/1.73 m2 [65.8%with CKD stages 3 and 4]. 80% of patients had ophthalmologic examination and 52.8% antiplatelet treatment. Hb A1c was 7.3 +/- 1.3%, but the percentage of patients with glycated hemoglobin > 7% and 8% was 54.9 and 28.6% [only 50.2% had been seen by an endocrinologist in the last 6 months]. 52.8% of patients were treated with insulin and 44.1% with anti-diabetic drugs, although only 19.6% used the new anti-diabetic drugs. 61% of patients had an LDLc > 100 mg/dl (61% treated) and 44% had triglycerides (TG) > 150 mg/dl (72% treated). 95% of patients presented with hypertension (BP > or = 130/80 mmHg),91% were undergoing antihypertensive treatment (79.7% with angiotensin-converting enzyme inhibitors and / or angiotensin receptor blockers). 81% with microalbuminuria and 78%with established proteinuria were receiving anti-proteinuric treatment. Of the patients considered to be refractory to BP (>3 drugs), only 28.9% underwent ambulatory BP monitoring. Significant differences were observed between stages of diabetic nephropathy and glycated hemoglobin (HBA1c; p = 0.048), systolic blood pressure (SBP; p = 0.024), lipidic control (HDLc; p = 0.015 and TG; p = 0.034), anemia (Hb; p = 0.010) and CKD (creatinine and sMDRD; p = 0.000). The levels of compliance with the therapeutic objectives regarding lipid control (LDL < or = 100 mg/dl and TG< or = 150 mg/dl), BP < or = 130/80 mmHg and HbA1c < or =7% were 1 objective: 68%, 2 objectives: 21.8% and 3 objectives: only 4% of patients., Conclusions: According to the results of our study, only a reduced proportion of patients fulfilled the different therapeutic end-points indicated. Future measures will be directed at improving physician-patient relationships with the main aim of intensifying the therapeutic measures to attain better metabolic and blood pressure control, nephroprotection and prevention in the appearance of cardiovascular events.

Type 2 diabetes nephropathy is a multifactorial trait whose threshold or limit for the phenotypic expression depends on the additive effect of multiple loci and environmental factors that are specific to each population. After the sequencing of human genome more susceptibility loci through linkage studies and association have been found. The association studies showed involvement 69 loci, whereas genetic linkage studies involved 24 loci. Among environmental factors, genetically unknown foods and excessive consumption of beverages with sweeteners has been reported. However, despite wide evidence in the genetic component in the development of kidney damage, the environment participation is not evident in several perinatal studies. One of the approaches proposed given the genetic heterogeneity that influences nephropathy, are epistasis studies, which will become increasingly important in the upcoming years.

Background and Objective: To determine the prevalence of occult chronic kidney disease (CKD) and the associated clinical variables in patients with type 2 diabetes mellitus (DM-2)., Patients and Method: Observational, laboratory and cross-sectional study of patients with DM-2 from primary care settings. Demographic and anthropometric data, previous illnesses and measures of cardiovascular risk and kidney function were collected from electronic medical records. We determined the prevalence of occult CKD defined as patients with normal values of plasma creatinine (Cr) and reduced glomerular filtration rate (GFr) (< 60 ml/min/1,73 m(2)). The GFr was determined by the Modification of Diet in Renal Disease (MDRD) equation., Results: The sample consisted of 3,197 patients, the mean age was 67.7 years (SD = 11.7) and 53.9% were men. The prevalence of CKD according to the MDMR values was 16.6% (n = 532), of which 60.3% (n = 321) corresponded to occult CKD. 6.6% (n = 211) of the participants had CKD with high Cr values. Multivariate analysis showed an association of occult CKD with female sex (OR = 2.7; CI 95% = 1,83-3,99). Occult CKD was associated with age, blood pressure higher than 150/100 mm/Hg and with a history of ischemic heart disease, heart failure, peripheral arterial disease and dyslipemia., Conclusions: The prevalence of CKD is 16.6%, of which 60.3% (n = 321) corresponds to occult CKD. Female sex is associated with the presence of occult CKD., (Copyright 2009 Elsevier España, S.L. All rights reserved.)

The importance of the early detection of diabetic nephropathy is because it is a cardiovascular risk marker and it indicates the existence of vascular changes associated to an increase risk of having a cardiovascular event in diabetes mellitus type 1 (DM 1), as well as in type 2 (DM 2). Microalbuminuria is a risk factor for overall cardiovascular and coronary mortality in the patients with DM 1. Total mortality is increased in patients with DM 2 and microalbuminuria with a RR of 1.8, and it is related to microalbuminuria levels even below the considered normal range (20 microg/min and/or 30 mg/day). For this reason, the definition of microalbuminuria must be reviewed in the patients with DM 2. More studies are needed to confirm the predictive power of microalbuminuria in cardiovascular and coronary disease., (Copyright (c) 2009 Elsevier España, S.L. All rights reserved.)