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The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers.International Urology and Nephrology Nov 2023Sodium-glucose co-transporter-2 inhibitor (SGLT-2i) administration is associated with some concerns in regard to the increased risk of genital and urinary tract...
PURPOSE
Sodium-glucose co-transporter-2 inhibitor (SGLT-2i) administration is associated with some concerns in regard to the increased risk of genital and urinary tract infections (UTI) in kidney transplant recipients (KTR). In this study, we present the results of SGLT-2i use in KTR, including the early post-transplant period.
METHODS
Participants were divided into two groups: SGLT-2i-free diabetic KTR (Group 1, n = 21) and diabetic KTR using SGLT-2i (Group 2, n = 36). Group 2 was further divided into two subgroups according to the posttransplant prescription day of SGLT-2i; < 3 months (Group 2a) and ≥ 3 months (Group 2b). Groups were compared for development of genital and urinary tract infections, glycated hemoglobin a1c (HgbA1c), estimated glomerular filtration rate (eGFR), proteinuria, weight change, and acute rejection rate during 12-month follow-up.
RESULTS
Urinary tract infections prevalence was 21.1% and UTI-related hospitalization rate was 10.5% in our cohort. Prevalence of UTI and UTI-related hospitalization, eGFR, HgbA1c levels, and weight gain were similar between the SGLT-2i group and SGLT-2i-free group, at the 12-month follow-up. UTI prevalence was similar between groups 2a and 2b (p = 0.871). No case of genital infection was recorded. Significant proteinuria reduction was observed in Group 2 (p = 0.008). Acute rejection rate was higher in the SGLT-2i-free group (p = 0.040) and had an impact on 12-month follow-up eGFR (p = 0.003).
CONCLUSION
SGLT-2i in KTR is not associated with an increased risk of genital infection and UTI in diabetic KTR, even in the early posttransplant period. The use of SGLT-2i reduces proteinuria in KTR and has no adverse effects on allograft function at the 12-month follow-up.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Kidney Transplantation; Glycated Hemoglobin; Urinary Tract Infections; Proteinuria
PubMed: 37289399
DOI: 10.1007/s11255-023-03645-7 -
Journal of Veterinary Internal Medicine 2024Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in...
BACKGROUND
Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria.
OBJECTIVES
Investigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis.
ANIMALS
Twenty-nine shelter cats.
METHODS
Case-control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein-to-creatinine (UPC) and urine amyloid A-to-creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and liquid chromatography-mass spectrometry (LC-MS) of proteins were performed.
RESULTS
Twenty-nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6-12.7 vs 1.5; 0.6-3.1; P = .03) and UAAC ratios (median, 7.18 × 10 ; range, 23 × 10 -21.29 × 10 vs 1.26 × 10 ; 0.21 × 10 -6.33 × 10 ; P = .04) than unaffected cats. The SDS-AGE identified mixed-type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC-MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C-III was higher in cats with AA amyloidosis (median, 1.38 × 10 ; range, 1.85 × 10 -5.29 × 10 vs 1.76 × 10 ; 0.0 × 10 -1.38 × 10 ; P = .01). In the kidney, AA-amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05).
CONCLUSIONS AND CLINICAL IMPORTANCE
Renal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.
Topics: Cats; Animals; Creatinine; Case-Control Studies; Kidney; Amyloidosis; Proteinuria; Serum Amyloid A Protein; Cat Diseases
PubMed: 37991136
DOI: 10.1111/jvim.16920 -
International Journal of Biological... 2024Proteinuria is a common and important clinical manifestation of chronic kidney disease (CKD) and an independent risk factor for the progression of kidney disease. As a...
Proteinuria is a common and important clinical manifestation of chronic kidney disease (CKD) and an independent risk factor for the progression of kidney disease. As a component of the glomerular filtration barrier (GFB), podocyte plays a key role in the pathogenesis of glomerular diseases and proteinuria. However, the pathophysiology of glomerular diseases associated with mitochondrial function is incompletely understood. Here, we identified three novel mutations in , encoding a membrane protein in mitochondria, associated with multisystem manifestations including nephrotic proteinuria and kidney injury in two Chinese patients. Conditional podocyte-specific Mtx2 knockout (Pod-Mtx2-KO) mice present a series of podocyte and glomerular abnormalities from 8 weeks to old age, including microalbuminuria, glomerular mesangial hyperplasia, fusion and effacement of foot process. MTX2 deficiency impaired podocyte functions manifested by reductions of adhesion, migration and endocytosis, which were further restored by overexpression of MTX2. Moreover, MTX2 defects led to abnormal mitochondrial structure and dysfunction, evidenced with defects of complex I and III, increased production of reactive oxygen species (ROS), and decreased protein levels of Sam50-CHCHD3-Mitofilin axis in the mitochondrial intermembrane space bridging (MIB) complex which is responsible for maintaining mitochondrial cristae morphology. Collectively, these findings reveal that the normal expression of MTX2 in glomerulus plays an important role in the adhesion, migration, endocytosis, proliferation and other physiological functions of podocytes, which may be realized by maintaining the morphological structure and function of mitochondria. Abnormal expression of MTX2 can lead to mitochondrial dysfunction and structural abnormalities by Sam50-CHCHD3-Mitofilin axis in podocyte, which further induces podocyte injury, glomerular lesions and proteinuria.
Topics: Animals; Humans; Mice; Kidney Glomerulus; Mitochondrial Diseases; Mitochondrial Proteins; Podocytes; Proteinuria; Renal Insufficiency, Chronic
PubMed: 38250156
DOI: 10.7150/ijbs.89916 -
American Journal of Physiology. Renal... Sep 2023Prepubertal obesity is currently an epidemic and is considered as a major risk factor for renal injury. Previous studies have demonstrated that insulin resistance...
Prepubertal obesity is currently an epidemic and is considered as a major risk factor for renal injury. Previous studies have demonstrated that insulin resistance contributes to renal injury in obesity, independent of diabetes. However, studies examining the relationship between insulin resistance and renal injury in obese children are lacking. Recently, we reported that progressive renal injury in Dahl salt-sensitive (SS) leptin receptor mutant (SSmutant) rats was associated with insulin resistance before puberty. Therefore, the aim of the present study was to examine whether decreasing insulin resistance with metformin will reduce renal injury in SSmutant rats. Four-wk-old SS and SSmutant rats were separated into the following two groups: ) vehicle and ) metformin (300 mg/kg/day) via chow diet for 4 wk. Chronic administration of metformin markedly reduced insulin resistance and dyslipidemia in SSmutant rats. We did not detect any differences in mean arterial pressure between vehicle and metformin-treated SS and SSmutant rats. Proteinuria was significantly greater in SSmutant rats versus SS rats throughout the study, and metformin administration significantly reduced proteinuria in SSmutant rats. At the end of the protocol, metformin prevented the renal hyperfiltration observed in SSmutant rats versus SS rats. Glomerular and tubular injury and renal inflammation and fibrosis were significantly higher in vehicle-treated SSmutant rats versus SS rats, and metformin reduced these parameters in SSmutant rats. These data suggest that reducing insulin resistance with metformin prevents renal hyperfiltration and progressive renal injury in SSmutant rats before puberty and may be therapeutically useful in managing renal injury during prepubertal obesity. Childhood/prepubertal obesity is a public health concern that is associated with early signs of proteinuria. Insulin resistance has been described in obese children. However, studies investigating the role of insulin resistance during childhood obesity-associated renal injury are limited. This study provides evidence of an early relationship between insulin resistance and renal injury in a rat model of prepubertal obesity. These data also suggest that reducing insulin resistance with metformin may be renoprotective in obese children.
Topics: Rats; Animals; Rats, Inbred Dahl; Insulin Resistance; Metformin; Pediatric Obesity; Kidney; Proteinuria; Sodium Chloride, Dietary; Hypertension; Blood Pressure
PubMed: 37498548
DOI: 10.1152/ajprenal.00078.2023 -
The Cochrane Database of Systematic... Aug 2023Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause... (Review)
Review
BACKGROUND
Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017.
OBJECTIVES
To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.
SEARCH METHODS
We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE).
MAIN RESULTS
We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m, 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life.
AUTHORS' CONCLUSIONS
We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
Topics: Child; Adult; Humans; Adolescent; Hydroxyurea; Antisickling Agents; Acute Chest Syndrome; Captopril; Lisinopril; Creatinine; Anemia, Sickle Cell; Kidney Failure, Chronic; Proteinuria; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid
PubMed: 37539955
DOI: 10.1002/14651858.CD012380.pub3 -
Clinical and Experimental Nephrology Sep 2023In the primary analysis of the PREDICT trial, a higher hemoglobin target (11-13 g/dl) with darbepoetin alfa did not improve renal outcomes compared with a lower... (Randomized Controlled Trial)
Randomized Controlled Trial
Higher hemoglobin levels using darbepoetin alfa and kidney outcomes in advanced chronic kidney disease without diabetes: a prespecified secondary analysis of the PREDICT trial.
BACKGROUND
In the primary analysis of the PREDICT trial, a higher hemoglobin target (11-13 g/dl) with darbepoetin alfa did not improve renal outcomes compared with a lower hemoglobin target (9-11 g/dl) in advanced chronic kidney disease (CKD) without diabetes. Prespecified secondary analyses were performed to further study the effects of targeting higher hemoglobin levels on renal outcomes.
METHODS
Patients with an estimated glomerular filtration rate (eGFR) 8-20 ml/min/1.73 m without diabetes were randomly assigned 1:1 to the high- and low-hemoglobin groups. The differences between the groups were evaluated for the following endpoints and cohort sets: eGFR and proteinuria slopes, assessed using a mixed-effects model in the full analysis set and the per-protocol set that excluded patients with off-target hemoglobin levels; the primary endpoint of composite renal outcome, evaluated in the per-protocol set using the Cox model.
RESULTS
In the full analysis set (high hemoglobin, n = 239; low hemoglobin, n = 240), eGFR and proteinuria slopes were not significantly different between the groups. In the per-protocol set (high hemoglobin, n = 136; low hemoglobin, n = 171), the high-hemoglobin group was associated with reduced composite renal outcome (adjusted hazard ratio: 0.64; 95% confidence interval: 0.43-0.96) and an improved eGFR slope (coefficient: + 1.00 ml/min/1.73 m/year; 95% confidence interval: 0.38-1.63), while the proteinuria slope did not differ between the groups.
CONCLUSIONS
In the per-protocol set, the high-hemoglobin group demonstrated better kidney outcomes than the low-hemoglobin group, suggesting a potential benefit of maintaining higher hemoglobin levels in patients with advanced CKD without diabetes.
CLINICAL TRIAL REGISTRATION
Clinicaltrials.gov (identifier: NCT01581073).
Topics: Humans; Darbepoetin alfa; Anemia; Renal Insufficiency, Chronic; Kidney; Hemoglobins; Proteinuria; Neoplasms; Diabetes Mellitus
PubMed: 37289335
DOI: 10.1007/s10157-023-02362-w -
Journal of the American Society of... Jul 2024
Topics: Proteinuria; Humans; Kidney Tubules; Kidney Glomerulus; Animals
PubMed: 38652545
DOI: 10.1681/ASN.0000000000000357 -
Endocrine Nov 2023The prevalence of type 2 diabetes mellitus (T2DM) is increasing each year and has become one of the most prominent health concerns worldwide. Patients with T2DM are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of type 2 diabetes mellitus (T2DM) is increasing each year and has become one of the most prominent health concerns worldwide. Patients with T2DM are prone to infectious diseases, and urinary tract infections are also widespread. Despite a comprehensive understanding of urinary tract infection (UTI), there is a lack of research regarding primary prevention strategies for asymptomatic bacteriuria (ASB).
OBJECTIVE
To clarify the incidence and risk factors of asymptomatic urinary tract infection in patients with T2DM by meta-analysis to provide evidence for preventing UTI. Help patients, their families, and caregivers to identify the risk factors of patients in time and intervene to reduce the incidence of ASB in patients with T2DM. Fill in the gaps in existing research.
STUDY DESIGN
Meta-analyses were conducted in line with PRISMA guidelines.
METHODS
Eleven databases were systematically searched for articles about ASB in T2DM, and the retrieval time was selected from the establishment of the database to February 5, 2023. Literature screening, quality evaluation, and meta-analysis were independently performed by two researchers according to the inclusion and exclusion criteria, and a meta-analysis was performed using Stata 17.0.
RESULTS
Fourteen articles were included, including cohort and case-control studies. A meta-analysis of 4044 patients with T2DM was included. The incidence of ASB in patients with T2DM was 23.7%(95% CI (0.183, 0.291); P < 0.001). After controlling for confounding variables, the following risk factors were associated with ASB in patients with T2DM: age (WMD = 3.18, 95% CI (1.91, 4.45), I = 75.5%, P < 0.001), female sex (OR = 1.07, 95% CI(1.02, 1.12), I = 79.3%, P = 0.002), duration of type 2 diabetes (WMD = 2.54, 95% CI (1.53, 5.43), I = 80.7%, P < 0.001), HbA1c (WMD = 0.63, 95% CI (0.43, 0.84), I = 62.6,%. P < 0.001), hypertension (OR = 1.59, 95% CI (1.24, 2.04), I = 0%, <0.001), hyperlipidemia (OR = 1.66, 95% CI (1.27, 2.18), I = 0%, P < 0.001), Neuropathy (OR = 1.81, 95% CI (1.38, 2.37), I = 0%, P < 0.001), proteinuria (OR = 3.00, 95% CI (1.82, 4.95), I = 62.7%, P < 0.001).
CONCLUSION
The overall prevalence of ASB in T2DM is 23.7%. Age, female sex, course of T2DM, HbA1C, hypertension, hyperlipidemia, neuropathy, and proteinuria were identified as related risk factors for ASB in T2DM. These findings can provide a robust theoretical basis for preventing and managing ASB in T2DM.
Topics: Humans; Female; Bacteriuria; Diabetes Mellitus, Type 2; Incidence; Glycated Hemoglobin; Risk Factors; Urinary Tract Infections; Proteinuria; Hyperlipidemias; Hypertension
PubMed: 37599328
DOI: 10.1007/s12020-023-03469-6 -
Nutrients Jul 2023Diabetic nephropathy (DN) is a major complication of diabetes. Nonalcoholic fatty liver disease (NAFLD) is common in diabetes, and liver fibrosis is a prognostic risk...
Diabetic nephropathy (DN) is a major complication of diabetes. Nonalcoholic fatty liver disease (NAFLD) is common in diabetes, and liver fibrosis is a prognostic risk factor for NAFLD. The interaction between DN and liver fibrosis in NAFLD remains unclear. In 189 patients with DN and NAFLD who received an education course about diabetic nephropathy, liver fibrosis was evaluated using the fibrosis-4 (FIB-4) index. The association between the outcome of DN and changes in liver fibrosis was examined. The FIB-4 index was maintained at the baseline level in patients with improved DN, while it was increased in other patients. The ΔFIB-4 index was positively correlated with changes in albuminuria and proteinuria (ρ = 0.22, = 0.004). In a multivariate analysis, changes in albuminuria and proteinuria were associated with the ΔFIB-4 index ( = 0.002). Patients with a progressive FIB-4 index category from baseline to 5 years showed a lower event-free survival rate after 5 years than patients with an improved FIB-4 index category ( = 0.037). The outcome of DN is associated with changes in liver fibrosis in patients with diabetes, NAFLD and DN. Developing a preventive and therapeutic approach for these conditions is required.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Diabetic Nephropathies; Albuminuria; Liver Cirrhosis; Risk Factors; Liver; Diabetes Mellitus
PubMed: 37513666
DOI: 10.3390/nu15143248 -
The Journal of Rheumatology Oct 2023To investigate the effect of sex on the clinical characteristics, prognoses, and therapeutic selection of eosinophilic granulomatosis with polyangiitis (EGPA).
OBJECTIVE
To investigate the effect of sex on the clinical characteristics, prognoses, and therapeutic selection of eosinophilic granulomatosis with polyangiitis (EGPA).
METHODS
We retrospectively enrolled 170 hospitalized patients with EGPA who were managed at our hospital between 2007 and 2020. Detailed clinical data were reviewed. Manifestations, prognoses, treatments, and outcomes were compared between female and male patients. Cumulative survival rates were calculated using Kaplan-Meier curves.
RESULTS
In this cohort, the male to female ratio was 1.4:1. Renal involvement was more frequent in male patients, including serum creatinine elevation, and proteinuria > 1 g/24 h. Severe gastrointestinal (GI) involvement occurred more commonly in male patients. Female patients had longer allergy duration and higher ratios of allergic rhinitis and asthma. Sex differences in proteinuria > 1 g/24 h, serum creatinine > 150 mmol/L, severe GI involvement, and weight loss were more significant in patients aged ≤ 55 years than those in patients aged > 55 years. Overall, male patients had a higher Birmingham Vasculitis Activity Score and a worse prognosis assessed at diagnosis, with a lower proportion of 1996 Five Factor Score = 0 than females. Regarding treatment selection, methylprednisolone pulse and cyclophosphamide were administered more frequently to male patients. All-cause mortality and cumulative survival rates were comparable between the sexes.
CONCLUSION
In this Chinese EGPA cohort, male and female patients showed distinct disease phenotypes. Male patients with EGPA had a higher disease activity at diagnosis and required more aggressive treatment for remission induction.
Topics: Humans; Male; Female; Granulomatosis with Polyangiitis; Retrospective Studies; Churg-Strauss Syndrome; Sex Characteristics; Creatinine; Proteinuria; Antibodies, Antineutrophil Cytoplasmic
PubMed: 37263648
DOI: 10.3899/jrheum.2022-1117