Diabetic Kidney Disease Patients Research Articles

Serum uric acid levels and diabetic kidney disease in patients with type 2 diabetes mellitus: A dose-response meta-analysis

ObjectiveOur study aimed to assess the existing evidence on whether serum uric acid (SUA) levels are associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). MethodsWe conducted a systematic search of articles up to October 2021 in Medline, Embase, The Cochrane Library and Web of Science that estimated DKD by SUA levels in patients with T2DM. Pooled relative risks with 95% CI were calculated using random effects models ResultsA total of eight cohort studies involving 25,741 T2DM patients were included. Meta-analysis showed that compared the highest with the lowest category of SUA level, the summary risk ratios were 2.04 (95%CI 1.43–2.92, P < 0.001). The linear dose-response analysis revealed that the risk of DKD increased by 24% for each 1 mg/dl increase of SUA. The non-linear dose-response analysis also showed a significant relevance between SUA and the risk of DKD in patients with type 2 diabetes mellitus (P < 0.001). ConclusionsSerum uric acid is associated with an increased risk of diabetic kidney disease in patients with type 2 diabetes mellitus. Serum uric acid level could be a good indicator for predicting diabetic kidney disease in patients with type 2 diabetes mellitus.

Effects of Systematic Diet Education Combined with Multidisciplinary Nursing on Nutritional Status and Calcium and Phosphorus Metabolism in Patients with Diabetic Kidney Disease in Uremic Phase after Treatment with Alogliptin.

Objective To explore the effects of systematic diet education combined with multidisciplinary nursing on nutritional status and calcium and phosphorus metabolism in patients with diabetic kidney disease (DKD) in uremic phase after treatment with alogliptin. Methods A total of 90 DKD patients with uremia admitted to our hospital from January 2020 to January 2021 were selected as the research objects. The subjects were divided into combined group and routine group by random number table method. All patients received alogliptin medication. The combination group received systematic dietary education combined with multidisciplinary nursing after the medication, and the conventional group received conventional intervention. Serum albumin, blood calcium, and other indexes were detected between both groups after intervention. Results After intervention, compared with the conventional group, all nutritional indexes of the combined group were obviously higher, levels of serum phosphorus and calcium-phosphorus product of the combined group were obviously lower (P < 0.001), the incidence of hypoglycemia and hyperglycemia of the combined group was obviously lower (P < 0.05), the total compliance rate of the combined group was obviously higher (P < 0.05), and the SAS score of the combined group was obviously lower (P < 0.001). Conclusion With conspicuous intervention effect, systematic diet education combined with multidisciplinary nursing is a reliable method that can improve the nutritional status and levels of calcium and phosphorus metabolism, enhance treatment compliance, and reduce anxiety. Further research will help to provide a better solution for patients. This trial is registered with ChiCTR2200057011.

Exploring molecular targets in diabetic kidney disease.

Diabetic kidney disease is the leading cause of end-stage kidney disease, and it remains a major challenge. Many factors, such as glomerular hyperfiltration, oxidative stress, inflammation, hypoxia, and epigenetics, are associated with the progression of diabetic kidney disease; however, the whole mechanism is not yet completely understood. No specific treatment for diabetic kidney disease has been established, so new approaches are being explored extensively. Sodium-glucose cotransporter 2 inhibitors have shown renoprotective effects in several human clinical trials. Glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported to be effective in diabetic kidney disease, and novel therapeutic candidates are also being examined. In the TSUBAKI trial, a nuclear factor erythroid 2-related factor 2 activator, bardoxolone methyl, improved the glomerular filtration rate of diabetic kidney disease patients. Similarly, new agents that act in the oxidative stress and inflammation pathways are of major interest, such as pentoxifylline, apoptosis signal-regulating kinase-1 inhibitors, C-C chemokine receptor 2 inhibitors, and Janus kinase-1/2 inhibitors. Endothelin-1 receptor A antagonists and soluble guanylate cyclase stimulators are also expected to affect renal hemodynamics. Some preclinical studies suggest that hypoxia-inducible factor prolyl hydroxylase inhibitors, which influence multiple inflammations and oxidative stress pathways, reduce albuminuria in diabetic kidney disease. Advanced glycation end-product inhibitors and treatments related to epigenetics have also shown promise as potential diabetic kidney disease treatments in preclinical studies. The discovery of new targets could provide new therapeutic options for overcoming diabetic kidney disease.

Intelligent Algorithm-Based Ultrasound Image for Evaluating the Effect of Comprehensive Nursing Scheme on Patients with Diabetic Kidney Disease.

This study was aimed at exploring the effect of ultrasound image evaluation of comprehensive nursing scheme based on artificial intelligence algorithms on patients with diabetic kidney disease (DKD). 44 patients diagnosed with DKD were randomly divided into two groups: group A (no nursing intervention) and group B (comprehensive nursing). In the same period, 32 healthy volunteers were selected as the control group. Ultrasonographic images based on the K non-local-means (KNL-Means) filtering algorithm were used to perform imaging examinations in healthy people and DKD patients before and after care. The results suggested that compared with those of the SAE reconstruction algorithm and KAVD reconstruction algorithm, the PSNR value of artificial bee colony algorithm reconstruction of image was higher and the MSE value was lower. The resistant index (RI) of DKD patients in group B after nursing was 0.63 ± 0.06, apparently distinct from the RI of the healthy people (controls) in the same group (0.58 ± 0.06) and the RI of DKD patients in group A (0.68 ± 0.07) (P < 0.05). The incidence rate of complications in DKD patients in group B was apparently inferior to that in group A. After comprehensive nursing intervention (CNI), the scores of all dimensions of quality of life (QoL) in DKD patients in group B were obviously superior versus those in DKD patients in group A. It suggests that implementation of nursing intervention for DKD patients can effectively help patients improve and control the level of renal function, while ultrasound images based on intelligent algorithm can dynamically detect the changes in the level of renal function in patients, which has the value of clinical promotion.

The dire need for improved management of chronic kidney disease: Associated hypertension in Pakistan.

Chronic Kidney Disease (CKD) refers to various kidney disorders ranging from mild to severe chronic kidney failure. Because of its escalating incidence and mortality rates, CKD is a serious public health concern in Pakistan. According to a study published in 2018, the overall prevalence of CKD among Pakistani adults was 21.2%, the highest in South Asia. (1) Although there are numerous risk factors for CKD, such as diabetes, cardiovascular disease, smoking, obesity, and genetics, hypertension poses the most serious threat, as the global prevalence of CKD-associated hypertension is between 60 – 90%. (2) In most people with CKD, proteinuria is observed in conjunction with hypertension. (3) As per the Kidney Disease Outcomes Quality Initiative (KDOQI) recommendations, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) are the preferred treatment choices for diabetic kidney disease and non-diabetic kidney disease patients with proteinuria. In 2013, a cross-sectional study conducted in Karachi, Pakistan, revealed that only 46.1% of General Practitioners opted for ACE inhibitors and ARBs as primary treatment for hypertension and proteinuria associated with CKD. (4) A randomized crossover trial conducted in March 2021 compared candesartan’s antihypertensive and antiproteinuric effects and the newest ARB, azilsartan medoxomil. The study results revealed that azilsartan (20 mg daily) treatment significantly decreased proteinuria and blood pressure without a noticeable increase in side effects than candesartan (8 mg daily) in patients with CKD who required antihypertensive drugs. (5) Considering the high prevalence of CKD in Pakistan, doctors must follow KDOQI guidelines and prescribe ARBs as the primary therapeutic agents for hypertensive patients with CKD. Azilsartan, the most recent ARB, has been proven to have the most potent antihypertensive and antiproteinuric benefits with the fewest side effects. (5) Therefore, physicians should encourage CKD patients to use azilsartan instead of candesartan and other classes of ARBs. Furthermore, improved screening techniques for CKD must be introduced and implemented so that doctors can manage the disease more effectively before it progresses into its final stages. Such screening tests would also help to improve blood pressure control among patients recognized to have CKD. Therefore, Pakistan’s public health sector should ensure the implementation of Kidney Disease Improving Global Outcomes (KDIGO) criteria to screen and manage CKD and CKD-associated hypertension and diabetes. Lastly, there is a dire need for awareness programs to educate general health practitioners regarding CKD management and the benefits of timely referral to a nephrologist.

Compositional Alterations of Gut Microbiota in Patients with Diabetic Kidney Disease and Type 2 Diabetes Mellitus

PurposeEmerging evidence has revealed that gut microbiota plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). However, few studies have used metagenomic sequencing to analyze the alterations of gut microbiota community in patients with early-stage DKD.MethodsWe carried out metagenomic sequencing in fecal samples of 10 DKD patients (DKD group) and 10 T2DM patients who appeared to be less prone to DKD (non-DKD group), aiming to compare the composition and function of gut microbiota between the DKD and non-DKD groups.ResultsThe gut microbial community of the DKD group was significantly different from that of the non-DKD group, characterized by a marked increase in phylum Proteobacteria, genus Selenomonadales, Neosynechococcus, Shigella, Bilophila, Acidaminococcus, species, Escherichia coli, Bacteroides plebeius, Megasphaera elsdenii, Acidaminococcus unclassified, and Bilophila wadsworthia. The amounts of species Citrobacter farmeri and Syntrophaceticus schinkii were significantly and positively correlated with the urinary albumin creatinine ratio in the DKD group. Furthermore, functional analysis based on dbCAN and KEGG databases showed aberrant lipopolysaccharide (LPS) biosynthesis and carbohydrate metabolism in the gut microbiome of the DKD group.ConclusionOur findings provided evidence for alterations in the composition and function of gut microbiota in patients with DKD versus the non-DKD group. These data may contribute to a more comprehensive understanding of the pathological mechanisms of DKD.

Association between COL4A3 variant rs55703767 and susceptibility to diabetic kidney disease in patients with type 2 diabetes mellitus: results from the INDEED cohort study.

Association between COL4A3 variant rs55703767 and susceptibility to diabetic kidney disease in patients with type 2 diabetes mellitus: results from the INDEED cohort study.

Validation of Two Asian Noninvasive Risk Models for Predicting Prevalent Undiagnosed Chronic Kidney Disease in Diabetic Patients Receiving Care at a Reference Hospital in A Sub-Saharan African Country: A Cross-Sectional Study.

Undiagnosed chronic kidney disease (CKD) is common in people with diabetes mellitus. Validated noninvasive risk models are an attractive CKD screening option in diabetic patients to identify patients who are more likely to be diagnosed with CKD via biological tests. The study aimed to validate the Korean and Thai noninvasive CKD risk prediction models in African Type 2 diabetic patients. This was a hospital-based study. The Modification of Diet in Renal Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations were used to estimate the glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 mL/min/1.73 m2, and any nephropathy as eGFR <60 mL/min/1.73 m2 and/or proteinuria. Discrimination was assessed and compared using c-statistics and non-parametric methods. Calibration performance was assessed before (original models) and after intercept adjustment. A total of 733 patients (421 men) aged 57.0 years (standard deviation = 10.4) were included. The MDRD equation identified 223 (30.4%) participants as having CKD and 377 (51.4%) participants with any nephropathy. The CKD-EPI equation identified fewer cases of CKD and any nephropathy with 194 (26.5%) and 357 (48.7%) cases, respectively. The original Korean model had the highest C-statistics of 0.696 (95% confidence interval: 0.654-0.739) for the outcome of eGFR <60 mL/min/1.73 m2 (using the CKD-EPI equation). Discrimination was significantly better in men, older and overweight participants. Intercept adjustment markedly improved calibration. Asian models have modest discrimination and good calibration with modest adjustment in predicting undiagnosed CKD in African diabetic patients; limiting their consideration for use in diabetes care in this setting.

POS-007 ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II (APACHE II) SCORING IS A PREDICTOR FOR ACUTE KIDNEY INJURY IN POLYTRAUMA PATIENTS

Trauma patients are at risk of acute kidney injury (AKI), which may be explained by renal hypoperfusion, rhabdomyolysis, direct renal injury, or the nephrotoxic effects of therapies in these patients, who survive their initial injuries and are associated with poor outcomes and higher mortality rates. The current study aimed to identify the predictors of AKI in polytrauma patients to prevent its occurrence and to improve the management of those critical patients. This is a prospective observational and analytical study. It was conducted on 300 polytrauma patients in Mansoura University Emergency Hospital (MUEH), Egypt, with the exclusion of diabetic and chronic kidney disease patients. APACHE II, Glasgow Coma Score (GCS), and Injury Severity Score (ISS) were evaluated with other routine laboratory data for every patient. Serum creatinine was repeated every 24 hours to assess the presence of AKI and determine the stage according to AKIN criteria. The frequency of AKI development among the polytrauma patients was (23.7%); including 50.7% with stage 1 AKI; 32.4% with stage 2 AKI and 16.9% with stage 3 AKI. Univariate analysis showed that low GCS, high ISS, high APACHE II score, high initial lactate, and high initial serum creatinine were risk factors for AKI in trauma patients. While multivariate analysis revealed only APACH II risk stratification scoring and the initial serum creatinine at admission were independent predictors for AKI development in polytrauma patients. Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring and initial serum creatinine are predictors for acute kidney injury in polytrauma patients.

POS-362 DEVELOPMENT OF BIOMARKERS FOR PREDICTING DKD PROGRESSION IN NON-PROTEINURIC TYPE 2 DIABETES: THE NTUH-DKD COHORT STUDY

Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Despite being a diagnostic criterion for DKD, the predictive value of urine albumin-creatinine ratio (UACR) on the progression toward advanced CKD is limited, due to the heterogeneous disease nature. Better predictive biomarkers are urgent needed to help us to better manage DKD patients. In this prospective cohort study, we evaluated the potential of incorporating a novel DKD Biomarker, a post-Translational Modification (PTM) fragment of Fetuin-A, into clinical parameters for predicting short-term DKD Progression in non-proteinuric type 2 diabetes (T2DM).

POS-331 L-carnitine ameliorates diabetic kidney disease by alleviating mitochondrial abnormality and fatty acid accumulation in SDT-fatty rats

Abnormal fatty acid metabolism is associated with the progression of diabetic kidney disease (DKD). Carnitine plays a central role in fatty acid β-oxidation and energy production by transporting long-chain fatty acids from the cytoplasm to the mitochondria. Recently, we found that significant ectopic fat was accumulated in the kidney tissue in DKD patients compared with those in minimal change kidney disease patients independent of proteinuria levels, suggesting the abnormal carnitine dynamics in DKD. Juvenile visceral steatosis (jvs) mice, described as an animal model for systemic carnitine deficiency caused by a mutation in slc22a5 gene, introduce a marked ectopic fat accumulation in the kidney. These findings suggest that abnormal carnitine dynamics in DKD cause ectopic fat accumulation due to abnormality of the fatty acid metabolism. However, the association between abnormalities of carnitine metabolism and the progression of DKD is unknown. Therefore, we investigated the kinetics of carnitine and the effect of L-carnitine therapy in type 2 DKD model rats. Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model was used. Unilateral nephrectomy was performed and 0.3% salt water was administered at 6 weeks of age, and created a renal dysfunction model in SDT fatty rat (DKD model). Age-matched male Sprague-Dawley (SD) rat was used as a control. Experiment 1: We compared 3 groups; ①SD rats (n=8) ②SDT fatty rats (n=8) ③DKD rats (n=8). Experiment 2: We compared 3 groups; ①SD rats with sham operation (n=8) ②DKD rats (n=7) ③DKD rats treated with L-carnitine administration (0.75% L-carnitine diet) for 10 weeks (n=6). All rats were sacrificed at 17 weeks old. Carnitine was measured by the enzyme cycling method. Acylcarnitine was analyzed by the tandem-mass spectrometry. Plasma and renal free carnitine levels were significantly decreased and long-chain acylcarnitine levels were significantly increased in DKD rats compared with those in SD and SDT fatty rats. The renal expression levels of organic cation / carnitine transporter 2 (OCTN2), carnitine palmitoyl transferase 1a (CPT1a), CPT2 and carnitine acetyltransferase (CrAT) were significantly decreased in DKD rats compared with those in SD and SDT fatty rats. Similarly, acetyl-CoA carboxylase (ACC) activity was significantly increased and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α) and peroxisome proliferator-activated receptor α (PPARα) activity were decreased in DKD rats. Further, marked ectopic fat accumulation in the renal tubules and glomeruli in DKD model rats was observed. L-carnitine administration significantly improved renal function, urinary albumin excretion, interstitial fibrosis and renal ectopic fat accumulation in DKD model rats. L-carnitine administration ameliorated the decrease of renal OCTN2, CPT1a, CPT2 and CrAT protein expression, and significantly improved ACC, PGC1α, and PPARα activity in DKD model rats. Furthermore, L-carnitine administration mitigated lipid peroxidation and mitochondrial dysfunction in DKD rats Abnormal carnitine kinetics and dynamics might play an important role in the progression of DKD. L-carnitine administration might be a promising therapeutic strategy for improving renal function by alleviating mitochondrial dysfunction in DKD rat model.

Association of chemotactic cytokine receptor 5 (CCR5) gene polymorphism (59029 A/G, rs1799987) with diabetic kidney disease in patients with type 2 diabetes from Poland.

Diabetic kidney disease (DKD) pathogenesis is multifactorial and is a combination of metabolic, genetic, and environmental factors. Due to a long period of asymptomatic course, it is often diagnosed late when advanced stages of the disease are present. Among patients with diabetes, the presence of chemotactic cytokine receptor 5 (CCR5) gene polymorphism is suspected to be associated with the risk of DKD occurrence; however, the results of the research conducted so far are inconclusive. The aim of this study was to evaluate the CCR5 gene polymorphism (rs1799987, 59029 A/G) association with DKD among patients with type 2 diabetes mellitus (T2DM), who are residents of the Upper Silesia region of Poland. CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among consecutive patients with type 2 diabetes mellitus (T2DM) treated in a single outpatient diabetology clinic in Upper Silesia, Poland. Its association with DKD was examined. Additionally, selected clinical and demographic data were included in the analysis. Among 467 eligible study patients, there was no association between examined CCR5 gene polymorphism and the presence of DKD in relation both to the American Diabetes Association definition (p = 0.6) and to the National Kidney Foundation definition (p = 0.3) of this complication. The presented study did not confirm the association between the examined gene polymorphism and the risk of DKD; further studies in this area are needed in order to establish or explicitly exclude this association.

Resveratrol ameliorates diabetic kidney injury by reducing lipotoxicity and modulates expression of components of the junctional adhesion molecule-like/sirtuin 1 lipid metabolism pathway

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, and previous studies have shown that lipid deposits in the kidneys can lead to diabetic kidney damage. Resveratrol reduces circulating glucose and lipid concentrations, but it is unknown whether it can reduce renal lipid deposition and lipotoxic damage by regulating local lipid metabolism. We first showed that abnormal lipid metabolism is closely related to DKD in patients. There were excessive lipid deposits in the kidneys of patients with various stages of DKD, alongside abnormal expression of the junctional adhesion molecule-like (JAML)/sirtuin 1 (Sirt1) lipid synthesis pathway (P < 0.05). Next, we fed C57BL/6J mice a high-fat diet for 12 weeks, which caused an increase in body mass, blood glucose concentration, and blood lipid concentrations; and abnormalities in renal function (P < 0.05). Resveratrol administration ameliorated the defects in circulating lipid and glucose concentrations, renal dysfunction, the renal expression of components of the JAML/Sirt1 lipid synthesis pathway, and the expression of the adipose differentiation-related protein in the mice (P < 0.05). Histological staining also showed less lipid deposition and kidney damage. Thus, resveratrol regulates the JAML/Sirt1 lipid synthesis pathway, reduces lipid deposition in the kidney, and ameliorates diabetic kidney damage.

The new Era of non-Steroidal Mineralocorticoid Antagonists in Treating Heart Failure in Diabetic Kidney Disease Patients.

Inappropriate activation of the mineralocorticoid receptor (MR) plays a significant role in developing hypertension, the development of cardiac pathological changes, and chronic kidney disease (CKD), where death related to cardiovascular (CV) causes is the primary competing for the outcome to the progress to end-stage renal disease (ESRD) in patients with CKD.&#x0D; Congestive heart failure (CHF) is a frequent comorbidity in patients with CKD. MR overactivation within the heart might cause coronary endothelial dysfunction, myocardial apoptosis, and reactive myocardial fibrosis and thus contribute to cardiac remodeling and its adverse consequences.&#x0D; MR antagonists (MRAs) are evidence-based therapy in symptomatic patients with heart failure and reduced ejection fraction (HFrEF).&#x0D; Finerenone, a novel, nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) with anti-inflammatory and antifibrotic effects, is a promising tool in treating heart failure in patients with T2DM and CKD.&#x0D; It is felt to have higher potency and less hyperkalemia than steroidal MRAs such as spironolactone and eplerenone. It is unclear and a matter of discussion if it could be first-line therapy in this group of patients.&#x0D; Conclusion: Nonsteroidal MRAs are currently tested in clinical trials. Based on preclinical and first clinical data, these nonsteroidal MRAs might overcome the limitations of today's steroidal antagonists.

Proteomic Analysis of Mouse Kidney Tissue Associates Peroxisomal Dysfunction with Early Diabetic Kidney Disease.

Background: The absence of efficient inhibitors for diabetic kidney disease (DKD) progression reflects the gaps in our understanding of DKD molecular pathogenesis. Methods: A comprehensive proteomic analysis was performed on the glomeruli and kidney cortex of diabetic mice with the subsequent validation of findings in human biopsies and omics datasets, aiming to better understand the underlying molecular biology of early DKD development and progression. Results: LC–MS/MS was employed to analyze the kidney proteome of 2 DKD models: Ins2Akita (early and late DKD) and db/db mice (late DKD). The abundance of detected proteins was defined. Pathway analysis of differentially expressed proteins in the early and late DKD versus the respective controls predicted dysregulation in DKD hallmarks (peroxisomal lipid metabolism and β-oxidation), supporting the functional relevance of the findings. Comparing the observed protein changes in early and late DKD, the consistent upregulation of 21 and downregulation of 18 proteins was detected. Among these were downregulated peroxisomal and upregulated mitochondrial proteins. Tissue sections from 16 DKD patients were analyzed by IHC confirming our results. Conclusion: Our study shows an extensive differential expression of peroxisomal proteins in the early stages of DKD that persists regardless of the disease severity, providing new perspectives and potential markers of diabetic kidney dysfunction.

Ketoanalogue Supplementation in Patients with Non-Dialysis Diabetic Kidney Disease: A Systematic Review and Meta-Analysis.

The effects of supplemental ketoanalogues (KA) in patients with diabetic kidney disease (DKD) are not well characterized. Several databases for peer-reviewed articles were systematically searched to identify studies reporting outcomes associated with the effects of a low-protein diet (LPD) or very-low protein diet (VLPD) in combination with supplemental KA in adults with DKD. Meta-analyses were conducted when feasible. Of 213 identified articles, 11 could be included in the systematic review. Meta-analyses for renal outcomes (4 studies examining glomerular filtration rate; 5 studies examining 24-h urinary protein excretion), metabolic outcomes (5 studies examining serum urea; 7 studies examining blood glucose), clinical outcomes (6 studies examining blood pressure; 4 studies examining hemoglobin), and nutritional outcomes (3 studies examining serum albumin; 4 studies examining body weight) were all in favor of KA use in DKD patients. Data from individual studies that examined other related parameters also tended to show favorable effects from KA-supplemented LPD/VLPD. The regimens were safe and well tolerated, with no evidence of adverse effects on nutritional status. In conclusion, LPD/VLPD supplemented with KA could be considered effective and safe for patients with non-dialysis dependent DKD. Larger studies are warranted to confirm these observations.

The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population.

The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

A Comparative Study of Acidosis in Diabetic Advanced Chronic Kidney Disease Patients on and off Metformin.

AimThe aim of the study is to assess the risk of acidosis in diabetic advanced chronic kidney disease (CKD) patients on and off metformin.MethodsThis retrospective descriptive study was conducted in the nephrology department in The Kidney Centre Post Graduate Training Institute (TKC PGTI) Karachi from February to April 2020. We reviewed the records of all patients over 18 years old who visited the nephrology outpatient department in three months in 2020 (from February 2020 to April 2020), who had CKD (stage 2-5), are not on dialysis, and had type 2 diabetes. These were divided into two groups: those on metformin for more than one year and those not on metformin. We looked at hospitalizations due to acidosis in the previous one-year period.ResultsA total of 524 CKD patients had diabetes; out of those, 268 patients were on metformin, and 256 were not on metformin. The male vs. female distribution was 52.1% vs. 47.9%. A total of 114 (21.8%) patients required admission in the previous one-year period, and only 12 hospitalized patients had acidosis, seven (58.3%) were on metformin, and five (41.7%) were not on metformin, which was statistically insignificant.ConclusionBiguanides, especially metformin, is a known oral hypoglycemic drug used for decades to treat type 2 diabetes mellitus (DM). Metformin use is related to a rare but serious adverse event, metformin-associated lactic acidosis (MALA), especially in renal failure patients. In our study, metformin use in CKD diabetic patients did not result in more admissions due to acidosis than non-metformin users.

PFKP Activation Ameliorates Foot Process Fusion in Podocytes in Diabetic Kidney Disease.

BackgroundGlycolysis dysfunction is an important pathogenesis of podocyte injury in diabetic kidney disease (DKD). Foot process fusion of podocytes and increased albuminuria are markers of early DKD. Moreover, cytoskeletal remodeling has been found to be involved in the foot process fusion of podocytes. However, the connections between cytoskeletal remodeling and alterations of glycolysis in podocytes in DKD have not been clarified.MethodsmRNA sequencing of glomeruli obtained from db/db and db/m mice with albuminuria was performed to analyze the expression profiling of genes in glucose metabolism. Expressions of phosphofructokinase platelet type (PFKP) in the glomeruli of DKD patients were detected. Clotrimazole (CTZ) was used to explore the renal effects of PFKP inhibition in diabetic mice. Using Pfkp siRNA or recombinant plasmid to manipulate PFKP expression, the effects of PFKP on high glucose (HG) induced podocyte damage were assessed in vitro. The levels of fructose-1,6-bisphosphate (FBP) were measured. Targeted metabolomics was performed to observe the alterations of the metabolites in glucose metabolism after HG stimulation. Furthermore, aldolase type b (Aldob) siRNA or recombinant plasmid were applied to evaluate the influence of FBP level alteration on podocytes. FBP was directly added to podocyte culture media. Db/db mice were treated with FBP to investigate its effects on their kidney.ResultsmRNA sequencing showed that glycolysis enzyme genes were altered, characterized by upregulation of upstream genes (Hk1, and Pfkp) and down-regulation of downstream genes of glycolysis (Pkm, and Ldha). Moreover, the expression of PFKP was increased in glomeruli of DKD patients. The CTZ group presented more severe renal damage. In vitro, the Pfkp siRNA group and ALDOB overexpression group showed much more induced cytoskeletal remodeling in podocytes, while overexpression of PFKP and suppression of ALDOB in vitro rescued podocytes from cytoskeletal remodeling through regulation of FBP levels and inhibition of the RhoA/ROCK1 pathway. Furthermore, targeted metabolomics showed FBP level was significantly increased in HG group compared with the control group. Exogenous FBP addition reduced podocyte cytoskeletal remodeling and renal damage of db/db mice.ConclusionsThese findings provide evidence that PFKP may be a potential target for podocyte injury in DN and provide a rationale for applying podocyte glycolysis enhancing agents in patients with DKD.

Biopsy Proven Kidney Disease From A Rural Tertiary Care Centre — A Social And Epidemiological Perspective

Abstract The prevalence of chronic kidney disease (CKD) is rising in rural areas. Screening of high risk cases, early detection and referral by the physicians reduces the prevalence of kidney disease in the population. Hereditary disorders, Glomerular diseases, Obstructive nephropathies are common causes in CKD in rural areas. Kidney biopsy is an essential diagnostic tool in to diagnose glomerular diseases. This prospective study done at tertiary care teaching hospital between 2017 and 2020 to understand the profile of glomerular diseases in rural area. Forty patients were included in the Study. Primary glomerular disease (PGD) was present in 26 patients and Secondary glomerular disease (SGD) in 10 and primary tubulointerstitial pathology in 4 patients. The most common Secondary glomerular disease was lupus. Glomerular diseases are amenable to immunomodulatory therapy leading to change in clinical outcome of the disease. However, Kidney biopsy is underutilized particularly in elderly patients, hypertensive nephropathy patients, suspected non diabetic kidney disease and lupus patients. Financial and social issues play dominant role in the treatment plan of chronic diseases in rural areas. Regional registry of kidney biopsy of urban and rural areas separately helps in paving a way of understanding the profile of glomerular diseases and its prevention.