Post-streptococcal acute glomerulonephritis in children:Association between proteinuria levels and renal outcomes

BACKGROUND Post-streptococcal acute glomerular nephritis(PSAGN)is mostly a benign condition.The usual sequelae of PSAGN include hypertension,its complications,and acute kidney injury.Severe PSAGN is associated with significant long-term morbidity,and histological abnormalities such as crescentic glomerulonephritis are infrequently reported.PSAGN has also been linked to late-onset chronic kidney disease in some populations due to high levels of proteinuria.METHODS This prospective observational study was conducted at Lady Ridgeway Hospital(Colombo,Sri Lanka)over 15 months.Children with PSAGN were enrolled based on clinical and laboratory criteria.Persistent proteinuria≥2+for 2 weeks and serum creatinine>100μmol/L warranted renal biopsy,assessed via light microscopy and immunofluorescence.Normalization of complement 3(C3)within 6 to 8 weeks was required for inclusion.Data on clinical features,urine protein levels,and renal function were collected from patient records,and potential associations were analysed using Statistical Package for the Social Sciences and R language for statistical computing.Ethical approval was obtained from the Ethical Review Committee,Lady Ridgeway Hospital for Children(Ref No:LRH/ERC/2021/60).RESULTS Forty-four patients were recruited.There were 27(61.4%)male patients and 17(38.6%)female patients.Thirty-seven(84%)of them were above 5 years of age.Twenty(45%)patients had a history of skin sepsis,and eighteen(41%)had a history of throat infection.Among patients with proteinuria≥2+,53%had serum creatinine>100µmol/L,while among those with proteinuria<2+,7%had serum creatinine>100µmol/L.The association of high-degree proteinuria with elevated serum creatinine was significant(χ²=7.8,P=0.005)in PSAGN.The odds ratio of the logistic regression model was 1.049(95%confidence interval:1.003-1.098),indicating a positive direction with statistically significant association(P=0.037).There was no significant association between proteinuria and the degree of hypertension or estimated creatinine clearance.Ten children underwent renal biopsy.Crescents(less than 50%)were demonstrated in five children,while three children had typical diffuse proliferative glomer-ulonephritis.One child had severe acute tubular necrosis,and another had crescentic glomerulonephritis(crescents>50%).The immunofluorescence studies revealed deposition of immunoglobulin G and C3 in all biopsy specimens.CONCLUSION High-degree proteinuria was significantly associated with elevated serum creatinine(>100μmol/L)in children with PSAGN.The majority of children with persistent proteinuria≥2+for more than 2 weeks and the highest recorded serum creatinine>100μmol/L had atypical renal histological findings.

Quality of life and psychological distress in end-stage renal disease patients undergoing hemodialysis and transplantation

BACKGROUND Among diverse profound impacts on patients’quality of life(QoL),end-stage renal disease(ESRD)frequently results in increased levels of depression,anxiety,and stress.Renal replacement therapies such as hemodialysis(HD)and transplantation(TX)are intended to enhance QoL,although their ability to alleviate psychological distress remains uncertain.This research posits the existence of a significant correlation between negative emotional states and QoL among ESRD patients,with varying effects observed in HD and TX patients.AIM To examine the relationship between QoL and negative emotional states(depression,anxiety,and stress)and predicted QoL in various end-stage renal replacement therapy patients with ESRD.METHODS This cross-sectional study included HD or TX patients in the Eastern Region of Saudi Arabia.The 36-item Short Form Survey and Depression Anxiety Stress Scale(DASS)was used for data collection,and correlation and regression analyses were performed.RESULTS The HD and TX transplantation groups showed statistically significant inverse relationships between QoL and DASS scores.HD patients with high anxiety levels and less education scored low on the physical component summary(PCS).In addition,the results of the mental component summary(MCS)were associated with reduced depression.Compared with older transplant patients,TX patients’PCS scores were lower,and depression,stress,and negative working conditions were highly correlated with MCS scores.CONCLUSION The findings of this study revealed notable connections between well-being and mental turmoil experienced by individuals undergoing HD and TX.The PCS of HD patients is affected by heightened levels of anxiety and lower educational attainment,while the MCS of transplant patients is influenced by advancing age and elevated stress levels.These insights will contribute to a more comprehensive understanding of patient support.

Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata:Systematic review and meta-analysis

BACKGROUND Gliflozins or Sodium glucose cotransporter 2 inhibitors(SGLT2i)are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients’cardiorenal outcomes.However,there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations.AIM To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction(LVEF)levels.METHODS Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels.Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations(NYHA)classifications for heart failure using Stata software version 17.0.RESULTS The literature search returned 13 Large clinical trials and 13 post hoc analysis reports.Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes,but higher efficacy were detected in patient groups at lower NYHA classifications(I2=46%,P=0.02).Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30%was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance(HR:0.70,95%CI:0.60 to 0.79 vs 0.81,95%CI:0.75 to 0.87;respectively,P=0.06).Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction(HFpEF)(HR:0.60,95%CI:0.49 to 0.72 vs 0.94,95%CI:0.74 to 1.13;P=0.04).Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF(HR:0.67,95%CI:51 to 0.82 vs 0.94,95%CI:0.82 to 1.06;P=0.01).Volume depletion was consistently increased in response to SGLT2i in all the subgroups.CONCLUSION Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins.Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.

Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes

Both GLP-1 receptor agonists(GLP-1RA)and SGLT-2 inhibitors(SGLT-2I)are newer classes of anti-diabetic agents that lower HbA1c moderately and decrease body weight and systolic blood pressure(SBP)modestly.Combination therapy with GLP-1RA plus SGLT-2I have shown a greater reduction in HbA1c,body weight,and SBP compared to either agent alone without any significant increase in hypoglycemia or other side effects.Since several agents from each class of these drugs have shown an improvement in cardiovascular(CV)and renal outcomes in their respective cardiovascular outcome trials(CVOT),combination therapy is theoretically expected to have additional CV and renal benefits.In this comprehensive opinion review,we found HbA1c lowering with GLP-1RA plus SGLT-2I to be less than additive compared to the sum of HbA1c lowering with either agent alone,although body weight lowering was nearly additive and the SBP lowering was more than additive.Our additional meta-analysis of CV outcomes with GLP1RA plus SGLT-2I combination therapy from the pooled data of five CVOT found a similar reduction in three-point major adverse cardiovascular events compared to GLP-1RA or SGLT-2I alone,against placebo.Interestingly,a greater benefit in reduction of heart failure hospitalization with GLP-1RA plus SGLT-2I combination therapy was noted in the pooled meta-analysis of two randomized controlled trials.Future adequately powered trials can confirm whether additional CV or renal benefit is truly exerted by GLP-1RA plus SGLT-2I combination therapy.

Renin-angiotensin system blockers-SGLT2 inhibitorsmineralocorticoid receptor antagonists in diabetic kidney disease:A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease(DKD)have been tested in patients with type 2 diabetes mellitus(T2DM)in the past two decades.With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001,no other pharmacological agent tested in the past two decades have shown any clinically meaningful result.Recently,the sodium-glucose cotransporter-2 inhibitor(SGLT-2i),canagliflozin,has shown a significant reduction in the composite of hard renal and cardiovascular(CV)endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of reninangiotensin system blocker use.Another SGLT-2i,dapagliflozin,has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease(CKD),regardless of T2DM status.Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM.However,the full results of this trial have not yet been published.While the use of older steroidal mineralocorticoid receptor antagonists(MRAs)such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes,a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM,with reasonably acceptable side effects.

Relook at DPP-4 inhibitors in the era of SGLT-2 inhibitors

SGLT-2 inhibitors(SGLT-2Is)have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases,heart failure,and diabetic kidney disease.Similarly,GLP-1 receptor agonists(GLP-1RAs)have significantly improved atherosclerotic cardiovascular outcomes.To this end,DPP-4 inhibitors(DPP-4Is)are cardiac-neutral drugs.While long-acting GLP-1RAs have shown a favorable HbA1c lowering compared to DPP-4Is,there is no clinically meaningful HbA1c lowering difference between SGLT-2Is vs DPP-4Is.Moreover,the glucose-lowering potential of SGLT-2Is gets compromised with a progressive decline in renal functions,unlike DPP-4Is.Furthermore,the HbA1c lowering potential of DPP-4Is is favorable in people with T2DM having a modest baseline HbA1c(8.0%-8.5%)compared with SGLT-2Is which lowers HbA1c larger in a background of higher baseline HbA1c(>8.5%-9.0%).These findings suggest that the role of DPP-4Is in the management of type 2 diabetes mellitus cannot be completely ignored even in the era of SGLT-2Is.