Effect of sodium-glucose transporter 2 inhibitor empagliflozin on proteinuria and kidney function progression in patients with non-diabetic glomerulonephritis: a pilot superiority randomized controlled trial.

BACKGROUND: Amelioration of proteinuria is one of main treatment targets in patients with glomerulonephritis, yet the remission rates are suboptimal. AIM OF THE STUDY: To examine the effect of the sodium-glucose transporter 2 inhibitor (empagliflozin) on proteinuria and kidney function progression, in patients with glomerulonephritis not due to diabetic kidney diseases. SUBJECTS AND METHODS: Fifty patients were recruited. The entry criteria were diagnosis of glomerulonephritis, and proteinuria (proteinuria ≥ 500 mg/g) in spite of the use of the maximal tolerated dose of RAAS blocking agents together with specific immunosuppression treatment regimens. Group 1 (Empagliflozin arm): 25 patients who received 25 mg of empagliflozin once daily for 3 months as add-on to their regular treatment protocol (RAAS blockers and immunosuppression). Group 2 (Placebo arm): 25 patients treated with RAAS blockers and immunosuppression. The primary efficacy endpoints were the change in creatinine eGFR, and proteinuria 3 months after starting treatment. RESULTS: Progression of proteinuria was lower with empagliflozin as compared to placebo (odds ratio, 0.65; 95% CI, 0.55 to 0.72, p = 0.002). Decline in eGFR was lower with empagliflozin as compared to placebo; however, this was statistically not significant (odds ratio, 0.84; 95% CI, 0.82 to 1.2, p = .31). The percentage change in proteinuria was greater with empagliflozin as compared to placebo (median, - 77 (- 97-105) vs - 48 (- 80-117). CONCLUSION: Empagliflozin has a favorable effect on amelioration of proteinuria in patients with glomerulonephritis. Empagliflozin has tendency to preserve kidney function in patients with glomerulonephritis as compared to placebo; however, longer term studies are required.

Seasonal variation of lupus nephritis in a cohort of Egyptian patients.

INTRODUCTION: Systemic lupus erythematosus is an autoimmune multisystem disease; renal affection is one of its most common manifestations. The effect of environmental factors on lupus nephritis flares is not fully understood. METHODS: This is a retrospective study that included 200 patients with lupus nephritis flares. All patients had confirmed diagnosis of lupus nephritis on histopathological examination. Lupus nephritis flares were defined by either (1) nephritic flare: defined as increased proteinuria or serum creatinine concentration; abnormal urinary sediment or a reduction in creatinine clearance, or (2) proteinuria flare defined as persistent increase in proteinuria > 0.5-1.0 g/day after achieving complete remission; doubling to > 1 g/day after achieving partial remission. The time of renal flare (month of the year) was recorded to determine the effect of seasonal variation on lupus nephritis flares. RESULTS: The median age for the patients was 33 years (IQR = 13); 92% of patients were females. The median duration of lupus was 7 years (IQR = 6). The median serum creatinine was 1.4 mg/dl, median serum urea level was 32, and median UPCR was 2.4 gm/dl. The highest incidence of flares occurred in June (14%) and July (12.5%) (p = 0.003). CONCLUSION: Seasonal pattern of LN flare was observed in our study in Egyptian cohort of patients, with most flares observed during meteorological summertime. Larger studies are needed to confirm this seasonal pattern. Key Points • Flares of lupus nephritis are common in patients with systemic lupus erythromatosus. • A seasonal pattern of flares of lupus nephritis was observed in our study. This seasonal pattern has been observed by previous studies in variable ethnicities and variable climatic circumstances.

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Kidney Transplant Recipients with Post-transplant Diabetes Mellitus (PTDM)- a Systematic Review and Meta-Analysis.

BACKGROUND: Kidney transplant recipients may develop post-transplant diabetes mellitus (PTDM). Dipeptidyl peptidase 4(DPP-4) inhibitors are evolving agents in the management of patients with diabetes mellitus. AIM: To evaluate the efficacy and safety of DPP-4 inhibitors in the management of post-transplant diabetes mellitus (PTDM) in renal transplant recipients. METHODS: We performed a systematic search of the electronic databases using keys words and Mesh terms. Data were extracted and reviewed using structured proforma. A comprehensive review of the eligible studies was performed independently by each of two reviewers; conflicts were resolved by the third reviewer. The primary efficacy endpoint was the difference in glycosylated hemoglobin (HbA1c) comparing any of the DPP-4 inhibitors to either placebo or other hypoglycaemic agent. The primary safety endpoints were the worsening of graft functions and change in Tacrolimus trough level. We performed the Random effect model using standardised mean difference. RESULTS: We identified seven studies that were eligible for the systematic review; only one study compared Sitagliptin to insulin Glargine. One study involved head to head comparison of three DPP-4 inhibitors. The other five studies were pooled in the meta-analysis. DPP-4 inhibitors had a favourable glycemic effect as measured by HbA1c when compared to either placebo or oral anti-hyperglycemic medications (standardised mean difference in HbA1c = -0.993, 95% CI= -1.303 to -0.683, P=0.001). DPP-4 inhibitors use did not result in significant change in eGFR ((standardised mean difference = 0.147, 95% CI= -0.139 - 0.433, p=0.312).) nor Tacrolimus level (standardised Mean Difference= 0.152, 95% CI= -0.172 to 0.477, P=0.354). CONCLUSION: Current evidence supports the short term efficacy and safety of DDP-4 inhibitor agents in the management of post transplantation diabetes mellitus (PTDM) in kidney transplant recipients. However, more RCTs are required to investigate the long-term safety and efficacy of these agents in kidney transplant recipients.

The Prevalence and Causes of Non-adherence to Immunosuppressive Medications in Patients with Lupus Nephritis Flares.

BACKGROUND: Lupus nephritis is one of the major manifestations of SLE. Poor adherence to medications is an important cause of not achieving treatment targets. METHODS: We assessed patients' adherence to immune-suppressive medications in patients with Lupus nephritis using the Morisky, Green, and Levine (MGL) Adherence Scale. The aim was to study the effect of non-adherence on the occurrence of renal flares. RESULTS: We recruited 104 patients with lupus nephritis. Sixty-six patients had flares of LN. There was a high prevalence of non-adherence to medications (n=68). Patients who were non-adherent to treatment had more renal flares (p= 0.02). Duration of lupus since diagnosis was significantly higher in patients who had renal flares. Using regression analysis, non-adherence to medications was associated with 3.7 higher risk of developing a single renal flare and 4.9 higher risk of developing more than one renal flare. Causes of non-adherence were medications side effects in 43% of patients, financial issues in 31% or forgetfulness in 26%. CONCLUSION: Non-adherence to immunosuppressive medications has a high prevalence in patients with lupus nephritis and is correlated with the number of renal flares.

Preventing acute kidney injury and improving outcome in critically ill patients utilizing risk prediction score (PRAIOC-RISKS) study. A prospective controlled trial of AKI prevention.

BACKGROUND: Acute kidney injury (AKI) has significant impact on mortality and morbidity in critically ill patients. METHODS: A prospective controlled interventional pilot study composed of observation and intervention arms was run at two different Intensive care unit (ICU) sites. A recently validated risk prediction score was used to predict the AKI in critically ill patients at high risk of developing AKI. All patients with established AKI at the time of recruitment were excluded from the study. A package of early preventive measures, including an early nephrology review was applied to high risk patients in the intervention arm to prevent AKI development. RESULTS: We have recruited 108 patients at the intervention site and 98 patients at the observation site. The primary outcome measure was the AKI incidence. AKI incidence was significantly lower in the intervention arm than its incidence in the observation arm (11% vs 26%, p = 0.002). The median Time till recovery of AKI episodes was significantly lower in the intervention arm (3(1) vs. 5(2) days, p = 0.014) 0.30 day mortality was lower in the intervention arm, however, not statistically significant. CONCLUSION: Our pilot study showed that it was feasible to apply a simple risk score to implement early preventive measures to high risk patients, consequently, mitigating the risk of AKI development and reducing the time till recovery of AKI episodes. Multicentre studies are needed to confirm this favourable effect.

Effect of reducing medication regimen complexity on glycaemic control in patients with diabetes.

INTRODUCTION: Medication Regimen complexity is an important issue of patients care that needs to be addressed. The aim of this study is the safe reduction of regimens complexities. The effect of this intervention on glycemic control was assessed in this study. METHODS: Seventy eight patients were recruited to the study. The entry criteria were non optimal glycemic, non-adherence (as demonstrated by indirect tools), and polypharmacy. The only intervention was the safe reduction of medication regimen complexity. This was done in view of the best practice guidelines; to ensure that all comorbidities are treated with the optimum number of medications for the optimum duration. There was no change to hypoglycemic regimen. All patients, whose hypoglycemic regimen has changed after the recruitment, were excluded. The primary outcome measure was the change in HbA1c three months after the intervention. RESULTS: Reducing medications regimen complexities led to a significant improvement of HbA1c in the after phase compared to the before phase (mean HbA1c in the before phase was 7.7 ± 0.43% compared to 6.93 ± 0.4% in the after phase. Mean reduction in the HbA1c was 0.77 ± 0.23%, p values < 0.001). CONCLUSION: Medications regimen complexity constitutes a burden for patients with diabetes. Reducing such regimens might improve glycemic control in those patients. Further studies are needed to confirm this favourable effect on the glycemic control.

A Prospective Micro-costing Pilot Study of the Health Economic Costs of Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) prevalence in the UK is estimated to be approximately 20% of all emergency admissions. Complications of AKI have a huge impact on health care costs. Most studies that have researched the economic costs of AKI have used macro-level costing using national tariffs and applying this to hospital episode statistics. METHODS: The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) study was a pilot study that tested the provision of early specialist advice to improve outcomes for patients with AKI. As part of this prospective study, we undertook a health economics substudy that involved micro-costing to help more accurately define the total cost per patient. RESULTS: We found that the total cost of providing an AKI alert system and an outreach service (intervention group) was lower than current practice (control group) for patients with AKI. Overall, an episode of AKI that required inpatient care costs approximately £5000 over 12 months, which is somewhat higher than previous UK estimates. Although it was feasible to collect the required complex dataset needed to conduct a health economics analysis of an outreach service, significant amounts of time and resources needed to be dedicated to this endeavor. CONCLUSION: We showed that it is possible to demonstrate a clearer, more detailed picture of the prolonged economic costs of AKI for a health care system, as part of a substudy of a larger trial. A larger scale, randomized controlled trial of AKI outreach is needed, with a prospective full economic evaluation conducted alongside the trial.

Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) trial: the protocol for a large pilot study.

INTRODUCTION: Acute kidney injury (AKI) contributes to morbidity and mortality, and its care is often suboptimal and/or delayed. The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) study is a large pilot testing provision of early specialist advice, to improve outcomes for patients with AKI. METHODS AND ANALYSIS: This before and after study will test an Outreach service for adult patients with AKI, identified using the national algorithm. During the 2-month before phase, AKI outcomes (30-day mortality, need for dialysis or AKI stage deterioration) will be observed in the intervention and control hospitals and their respective community areas; no interventions will be delivered. Patients will receive good standard care. During the 5-month after phase, the intervention will be delivered to patients with AKI in the intervention hospital and its area. Patients with AKI in the control hospital and its area will continue to have good standard care only. Patients already on dialysis and at end of life will be excluded. The interventions will be initially delivered via a phone call, with or without a visit to the primary clinician, aiming at rapidly establishing the aetiology, correcting reversible causes and conducting further appropriate investigation. Surviving stage 3 patients will be followed-up in an AKI clinic. We will conduct qualitative research using focus group-based discussions with primary and secondary care clinicians during the early and late phases of the trial. This will help break down potential barriers and improve care delivery. ETHICS AND DISSEMINATION: Patients will be contacted about the study allowing them to 'opt out'. The work of an Outreach team, guided by AKI alerts and delivering timely advice to clinicians, may improve outcomes. If the results suggest that benefits are delivered by an AKI Outreach team, this study will lead to a full cluster randomised trial. TRIAL REGISTRATION NUMBER: NCT02398682: Pre-results.