Background: Better data are necessary to determine whether baseline level of kidney function affects the rate of progressive kidney disease following pregnancy. Objective: The objective was to determine whether the baseline (pre-pregnancy) estimated glomerular filtration rate (eGFR) modifies the association between becoming pregnant and the subsequent rate of progressive kidney disease. Design: Population-based cohort study using provincial administrative health care databases in Ontario and Alberta, Canada. Setting: The sample will be accrued from April 1, 2007, to March 31, 2023, in Ontario and from April 1, 2012, to March 31, 2023, in Alberta. Follow-up for study outcomes will occur until March 31, 2024. Participants: The pregnant group will include adult female residents of Ontario or Alberta with a record of a pregnancy of 20 to 46 weeks’ gestation during the accrual period, and the non-pregnant group will include adult female residents with no prior record of pregnancy. The cohort entry dates in those in the pregnant group will be the estimated date of conception; the entry dates for those in the non-pregnant group will be randomly assigned following the distribution of dates in the pregnant group. To be eligible, individuals must be between 18 and 45 years old at cohort entry. They require at least 1 serum creatinine measurement within 2 years before entry and should not have received maintenance dialysis or a prior kidney transplant. Both groups will be categorized into one of 3 levels of baseline eGFR (≥60, 45–59, and <45 mL/min per 1.73 m 2 ). Inverse probability of treatment weighting on a propensity score will be used to balance the pregnant and non-pregnant groups on baseline characteristics (including age, proteinuria, hypertension, and diabetes) within the 3 categories of baseline eGFR. Measurements: The primary outcome, progressive kidney disease, will be defined as a composite of a persistent ≥40% drop in eGFR from the baseline value, a new persistent eGFR <15 mL/min per 1.73 m 2 , receipt of maintenance dialysis, or receipt of a kidney transplant. The secondary outcomes will be the components of the primary composite outcome examined separately and the annualized change in eGFR in mL/min per 1.73 m 2 from baseline. Methods: We will test for statistical interaction to determine whether the baseline category of eGFR modifies the rate of long-term progressive kidney disease after pregnancy. We hypothesize that a statistical interaction will be present. We will present weighted cause-specific hazard ratios (HRs) and cumulative incidence function (CIF) curves for up to 10 years of follow-up for the pregnant and non-pregnant groups stratified by each eGFR category. We will perform additional pre-specified analyses to confirm whether the findings are robust and examine associations that account for baseline proteinuria. Results: Based on a feasibility analysis using ICES data in Ontario, we expect the cohort to include over 400 000 pregnant females and 1.2 million non-pregnant females. This includes at least 395 000 pregnant females with baseline eGFR ≥60 mL/min/1.73 m 2 , 300 with eGFR 45 to 59 mL/min/1.73 m 2 , and 110 with eGFR <45 mL/min/1.73 m 2 . The median follow-up is anticipated to be 5 years (range = 1-17 years) with minimal loss to follow-up. Limitations: Measures of kidney function will be obtained as part of routine care (not according to a research schedule). Measures of baseline proteinuria are frequently missing from routine care data, even in up to 15% of those with an eGFR <45 mL/min per 1.73 m 2 . Conclusion: This study will investigate whether the level of baseline eGFR modifies the rate of progressive kidney disease after pregnancy and will estimate the cumulative incidence of progressive kidney disease in pregnant and non-pregnant females across 3 categories of baseline eGFR.

Objectives:To highlight data on interventions aimed at enhancing referral patterns from primary care to nephrology. Design:Systematic review and meta-analysis. Data sources:MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science and PsycINFO. Eligibility criteria:Studies reporting interventions aimed at decreasing referral volume, reducing wait times and/or increasing guideline-concordant referrals in adult patients with chronic kidney disease from primary care to specialist kidney care, from inception to 15 April 2024. Data extraction and synthesis:Studies were subcategorised based on taxonomy of initiatives, type of intervention and single versus multi-faceted interventions. Our primary outcomes were changes to referral volume, wait times and proportion of guideline-concordant referrals. Data were pooled using a random effects model and a meta-analysis was conducted using pooled mean difference (MD) and OR. Results:20 studies used single and 13 used more than one intervention. Overall, interventions resulted in an increase in total referrals (MD: 19 referrals per month, 95% CI 7 to 30; I2=98%; p<0.001) and a non-significant decrease in the proportion of guideline-concordant referrals (OR: 0.32, 95% CI 0.09 to 1.16; I2=100%; p=0.08). These effects were consistent when stratified by single versus multi-faceted interventions, and by taxonomy of interventions. Interventions categorised as financial, regulatory or legislative incentives (n=2) led to an increase in guideline-concordant referrals (OR: 1.15, 95% CI 1.02 to 1.29; I2: 0%; p=0.02). Organisational changes showed a non-significant reduction in wait time of 24 days (95% CI -64 to 15, I2=99%; p=0.23) but tended to decrease guideline concordant referrals (OR: 0.17, 95% CI 0.03 to 0.86; I2: 100%; p=0.03). Conclusion:Organisational changes decreased wait times. Overall, interventions increased referral volume and decreased guideline-concordant referrals. The data have implications for designing programmes to improve primary care-nephrology interface in kidney disease management.

Connexin (Cx) 37, 40, and 43 are implicated in vascular function, specifically in the electrical coupling of endothelial cells and vascular smooth-muscle cells. In the present study, we investigated whether factors implicated in vascular dysfunction can modulate the gene expression of Cx37, Cx40, and Cx43 and whether this is associated with changes in endothelial layer barrier function in human microvascular endothelial cells (HMEC-1). First, HMEC-1 were subjected to stimuli for 4 and 8 h. We tested their responses to DETA-NONOate, H2O2, high glucose, and angiotensin II, none of which relevantly affected the transcription of the connexin genes. Next, we tested inflammatory factors IL-6, interferon gamma (IFNγ), and TNFα. IFNγ (10 ng/mL) consistently induced Cx40 expression at 4 and 8 h to 10–20-fold when corrected for the control. TNFα and IL-6 resulted in small but significant depressions of Cx37 expression at 4 h. Two JAK inhibitors, epigallocatechin-3-gallate (EGCG) (100–250 μM) and AG490 (100–250 μM), dose-dependently inhibited the induction of Cx40 expression by IFNγ. Subsequently, HMEC-1 were subjected to 10 ng/mL IFNγ for 60 h, and intercellular and transcellular impedance was monitored by electric cell-substrate impedance sensing (ECIS). In response to IFNγ, junctional-barrier impedance increased more than cellular-barrier impedance; this was prevented by AG490 (5 μM). In conclusion, IFNγ can strongly induce Cx40 expression and modify the barrier properties of the endothelial cell membrane through the JAK/STAT pathway. Moreover, the Cx37, Cx40, and Cx43 expression in endothelial cells is stable and, apart from IFNγ, not affected by a number of factors implicated in endothelial dysfunction and vascular diseases.

Objective: Oscillometric device accuracy may be decreased, and variability may be increased, in patients with chronic kidney disease. The objective of this study was to compare three oscillometric algorithms to identify which minimizes oscillometric blood pressure variability in chronic kidney disease. Design & Methods: Sixty patients with chronic kidney disease were studied. Thirty were on hemodialysis (HD group) and thirty had stage 3 chronic kidney disease (Stage 3 CKD). Baseline demographics and medical comorbidities were recorded. The mean of 3 readings from the Omron HEM 907XL device was used to provide a control (reference) blood pressure. Three oscillometric waveforms were also collected using a computer-based system, processed, and used to derive blood pressure by each of three algorithms: 1. simple fixed-ratio; 2. initial binning according to mean arterial pressure and then application of different fixed ratios within each bin (binning method); and 3. binning plus linear regression to incorporate the influence of additional oscillometric waveform characteristics (binning regression method). The mean of three blood pressure determinations from each algorithm was calculated and compared to the Omron mean, with variability assessed by calculating the standard deviation of the difference compared to the Omron. Results: Mean age in the overall group (± SD) was 65.6 ± 13.7 years (HD 63.4 ± 16.3 years; Stage 3 CKD 65.9 ± 10.7 years), percent female in the overall group was 42% (HD 37%; Stage 3 CKD 47%), and mean arm circumference overall was 31.5 ± 4.7 cm (HD 30.8 ± 4.4 cm; Stage 3 CKD 32.2 ± 5.0 cm. Hypertension was present in 82% of participants (HD 80%; Stage 3 CKD 83%). Mean Omron blood pressure was 136.9 ± 25.4/72.7 ± 15.8 mmHg. Compared to the Omron, the systolic/diastolic results for each algorithm were 134.4 ± 20.5/75.0 ± 12.9 for fixed ratio, 128.5 ± 19.8/71.4 ± 12.0 for binning, and 127.7 ± 18.7/70.2 ± 8.8 for binning regression (Table 1). Conclusions: An oscillometric algorithm based on simple fixed-ratio minimized variability in patients with chronic kidney disease. Manufacturers of devices designed for blood pressure measurement in this population should consider incorporating this approach into their algorithm-based blood pressure derivation.

Background: Autonomic nervous system (ANS) dysfunction and vascular stiffness increase cardiovascular risk in people with chronic kidney disease (CKD). Chronic elevations in sympathetic activity can lead to increased arterial stiffness; however, the relationship between these variables is unknown in CKD. Objective: To explore the association between measures of autonomic function and arterial stiffness in patients with moderate-to-severe CKD. Methods: This study was a prespecified secondary analysis of a randomized controlled trial. This included the following measures: 24-hour ambulatory blood pressure (BP), carotid-femoral and carotid-radial pulse wave velocity (PWV), and postexercise heart rate recovery (HRR). We used mixed effect linear regression models with Bayesian information criteria (BIC) to assess the contribution of ANS measurements. Results: Forty-four patients were included in the analysis. Mean carotid-femoral and carotid-radial PWV were 7.12 m/s (95% CI 6.13, 8.12) and 8.51 m/s (7.90, 9.11), respectively. Mean systolic dipping, calculated as percentage change in mean systolic readings from day to night, was 10.0% (95% CI 7.79, 12.18). Systolic dipping was independently associated with carotid-radial PWV, MD −0.09 m/s (95% CI −0.15, −0.02) and had the lowest BIC. Conclusions: Systolic dipping was associated with carotid-radial PWV in people with moderate-to-severe CKD; however, there was no association with carotid-femoral PWV. Systolic dipping may be a feasible surrogate of ANS function, as the association with carotid-radial PWV was consistent with the minimal clinically important difference (MCID). Future studies are needed to define the relationship between ANS function, arterial stiffness, and CV events over time in people with CKD.

Background and Objective: Bioimpedance technologies are increasingly used to determine fluid status in patients with chronic kidney disease and those with end-stage kidney disease on dialysis. We aimed to determine whether this technology improves clinical outcomes as compared with usual care. Methods: We performed a systematic review and meta-analysis of trials, comparing fluid management guided by bioimpedance technologies to standard of care in patients with chronic kidney disease. Our primary outcome was all-cause mortality. Secondary outcomes included blood pressure control, all-cause hospitalization, major adverse cardiovascular events, and change in left ventricular mass index. Results: Our search identified 819 citations of which 12 randomized controlled trials were included (2420 patients). No studies of non-dialysis-dependent chronic kidney disease patients met inclusion criteria. Mean age was 55 years and mean follow-up was 1 year. There was a statistically significant difference in all-cause mortality between both arms studied (risk ratio [RR] 0.64, 95% confidence interval [CI]: 0.44, 0.99). Better blood pressure control was observed in the bioimpedance arm of the included articles, weighted mean differences (WMD) −3.13 mm Hg (95% CI: −5.73, −0.53 mm Hg) for systolic blood pressure and WMD −2.50 mm Hg (95% CI: −4.36, −0.64 mm Hg) for diastolic blood pressure. No difference was observed concerning the other outcomes. Conclusions: Among patients on maintenance dialysis, bioimpedance-guided volume management showed decreased all-cause mortality and blood pressure but no significant difference in all-cause hospitalization, major adverse cardiac event, or change in left ventricular mass index. This may be due to a younger population sample than previous articles. Moreover, our study identified a knowledge gap by highlighting the lack of studies evaluating this technology in non-dialysis-dependent chronic kidney disease patients.

Background: The hypertension specialist often receives referrals of patients with young-onset, severe, difficult-to-control hypertension, patients with hypertensive emergencies, and patients with secondary causes of hypertension. Specialist hypertension care compliments primary care for these complex patients and contributes to an overall hypertension control strategy. The objective of this study was to characterize hypertension centres and the practice patterns of Cana-dian hypertension specialists. Methods: Adult hypertension specialists across Canada were surveyed to describe hypertension centres and specialist practice in Canada, including the following: the patient population managed by hyperten-sion specialists; details on how care is provided; practice pattern var-iations; and differences in access to specialized hypertension resources across the country. Results: The survey response rate was 73.5% from 25 hypertension centres. Most respondents were nephrologists and general internal medicine specialists. Hypertension centres saw between 50 and 2500 patients yearly. A mean of 17% (+/- 15%) of patients were referred from the emergency department and a mean of 52% (+/- 24%) were referred from primary care. Most centres had access to specialized testing (adrenal vein sampling, level 1 sleep studies, autonomic testing) and advanced therapies for resistant hypertension (renal denervation). Considerable heterogeneity was present in the target blood pressure in young people with low cardiovascular risk and in the diagnostic algo-rithms for investigating secondary causes of hypertension. Conclusions: These results summarize the current state of hyperten-sion specialist care and highlight opportunities for further collaboration among hypertension specialists, including standardization of the approach to specialist care for patients with hypertension.

Introduction: Tubuloglomerular feedback (TGF) is the negative feedback component of renal blood flow (RBF) autoregulation. Neighbouring nephrons often exhibit spontaneous TGF oscillation and synchronization mediated by endothelial communication, largely via connexin40 (Cx40). Methods: We had a knockout (KO) rat made that lacks Cx40. One base pair was altered to create a stop codon in exon 1 of Gja5, the gene that encodes Cx40 (the strain is WKY-Gja55em1Mcwi). Blood pressure (BP)-RBF transfer functions probed RBF dynamics and laser speckle imaging interrogated the dynamics of multiple efferent arterioles that reach the surface (star vessels). Results: The distribution of wild type (WT), heterozygote, and KO pups at weaning approximated the Mendelian ratio of 1:2:1; growth did not differ among the three strains. The KO rats were hypertensive. BP-RBF transfer functions showed low gain of the myogenic mechanism and a smaller TGF resonance peak in KO than in WT rats. Laser speckle imaging showed that myogenic mechanism had higher frequency in KO than in WT rats, but similar maximum spectral power. In contrast, the TGF frequency was similar while peak power of its oscillation was much smaller in KO than in WT rats. In WT rats, plots of instantaneous TGF phase revealed BP-independent TGF synchronization among star vessels. The synchronization could be both prolonged and widespread. In KO rats TGF synchronization was not seen, although BP transients could elicit short-lived TGF entrainment. Discussion: Despite the reduced TGF spectral power in KO rats, there was sufficient TGF gain to induce oscillations and therefore enough gain to be effective locally. We conclude that failure to synchronize is dependent, at least in part, on impaired conducted vasomotor responses.

Sporadic mechanically-induced hemolysis associated with kinks in extracorporeal blood circuits during hemodialysis is a rare but potentially serious complication that exhibits laboratory features consistent with both in vivo and in vitro hemolysis. Misclassification of clinically significant hemolysis as in vitro can lead to inappropriate test cancellation and delayed medical interventions. Here, we report three cases of hemolysis attributed to kinked hemodialysis blood lines, which we have defined as “ex vivo” hemolysis. All three cases demonstrated an initial mixed picture of laboratory features consistent with both classifications of hemolysis. Specifically, absent features of in vivo hemolysis on blood film smear despite normal potassium led to the misclassification of these samples as in vitro hemolysis and their cancellation. A proposed mechanism for these overlapping laboratory features is the recirculation of damaged red blood cells from the kinked or pinched hemodialysis line back into the patient circulation producing an “ex vivo” hemolysis presentation. In two of the three cases, the patients developed acute pancreatitis as a result of hemolysis and required urgent medical follow up. We developed a decision pathway to help laboratories in identifying and handling these samples by recognizing that in vitro and in vivo hemolysis have overlapping laboratory features. These cases highlight the need for laboratorians and the clinical care team to be vigilant about mechanically-induced hemolysis from the extracorporeal circuit during hemodialysis. Communication is critical to identify the cause of hemolysis in these patients and prevent unnecessary delays in result reporting.

This review paper considers the consequences of modulating tubular reabsorption proximal to the macula densa by sodium–glucose co-transporter 2 (SGLT2) inhibitors, acetazolamide, and furosemide in states of glomerular hyperfiltration. SGLT2 inhibitors improve renal function in early and advanced diabetic nephropathy by decreasing the glomerular filtration rate (GFR), presumably by activating the tubuloglomerular feedback (TGF) mechanism. Central in this paper is that the renoprotective effects of SGLT2 inhibitors in diabetic nephropathy can only be partially explained by TGF activation, and there are alternative explanations. The sustained activation of TGF leans on two prerequisites: no or only partial adaptation should occur in reabsorption proximal to macula densa, and no or only partial adaptation should occur in the TGF response. The main proximal tubular and loop of Henle sodium transporters are sodium–hydrogen exchanger 3 (NHE3), SGLT2, and the Na-K-2Cl co-transporter (NKCC2). SGLT2 inhibitors, acetazolamide, and furosemide are the most important compounds; inhibiting these transporters would decrease sodium reabsorption upstream of the macula densa and increase TGF activity. This could directly or indirectly affect TGF responsiveness, which could oppose sustained TGF activation. Only SGLT2 inhibitors can sustainably activate the TGF as there is only partial compensation in tubular reabsorption and TGF response. SGLT2 inhibitors have been shown to preserve GFR in both early and advanced diabetic nephropathy. Other than for early diabetic nephropathy, a solid physiological basis for these effects in advanced nephropathy is lacking. In addition, TGF has hardly been studied in humans, and therefore this role of TGF remains elusive. This review also considers alternative explanations for the renoprotective effects of SGLT2 inhibitors in diabetic patients such as the enhancement of microvascular network function. Furthermore, combination use of SGLT2 inhibitors and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs). in diabetes can decrease inflammatory pathways, improve renal oxygenation, and delay the progression of diabetic nephropathy.

BACKGROUND:Whether fluid overload is associated with vascular stiffness parameters in hemodialysis (HD) patients has not been fully elucidated. We hypothesized that interdialytic fluid accumulation increases vascular stiffness parameters, which improves with intradialytic ultrafiltration. METHODS:Fluid overload and vascular stiffness parameters were assessed in 39 HD patients (20 with and 19 without fluid overload) and compared to 26 healthy controls. Fluid status was assessed 15 minutes before the mid-week HD session by bio-impedance spectroscopy. Following this, ambulatory pulse wave velocity (PWV) and augmentation index (AIx) were measured for 24 hours before another mid-week HD session and then for 5 hours starting 30 minutes before and ending 30 minutes after the session. RESULTS:HD patients had significant fluid overload compared to healthy controls (2.0±2.4 vs. -0.2±0.6 L; P<0.001) and baseline PWV was higher (10.3±1.7 vs. 8.8±1.4 m/s; P<0.001). There was no significant difference between PWV and AIx in fluid overloaded and non-fluid overloaded HD patients prior to, or during the HD session. AIx of non-fluid overloaded HD patients improved after the HD session (P = 0.04). Average 24-hour AIx was higher in fluid overloaded HD patients (P<0.001). CONCLUSIONS:Inter- and intradialytic changes in fluid volume were only weakly related to vascular stiffness parameters in HD patients. Although there was a modest reduction in AIx in non-fluid overloaded HD patients after the dialysis session, fluid removal did not improve vascular stiffness parameters during the HD session. We speculate that the effect of fluid overload correction on vascular stiffness parameters requires long-term adjustments in the vasculature.

Background: Hypertension, together with poorly controlled blood pressure (BP) are known risk factors for kidney disease and progression to kidney failure as well as increased cardiovascular (CV) morbidity and mortality. Several studies in patients without kidney disease have demonstrated the efficacy of home BP telemonitoring (HBPT) for BP control. Objective: The primary aim of this study is to assess the mean difference in systolic BP (SBP) at 12 months, from baseline in remote dwelling patients with hypertension and chronic kidney disease (CKD) in Northern Alberta, Canada, comparing HBPT + usual care versus HBPT + a case manager. Other secondary objectives, including cost-effectiveness and acceptability of HBPT as well as occurrence of adverse events will also be assessed. Methods Design: This study is designed as a pragmatic randomized controlled trial (RCT) of HBPT plus clinical case management compared to HBPT with usual care. Setting: Peace River region in Northern Alberta Region, Canada. Patients: Primary care patients with CKD and hypertension. Measurements: Eligible patients will be randomized 1:1 to HBPT + BP case management versus HBPT + usual care. In the intervention arm, BP will be measured 4 times daily for 1 week, with medications titrated up or down by the study case manager until guideline targets (systolic BP [SBP]: <130 mmHg) are achieved. Once BP is controlled, (ie, to guideline-concordant targets), this 1-week protocol will be repeated every 3 months for 1 year. Patients in the control arm will also follow the same BP measurement protocol; however, there will be no interactions with the case manager; they will share their BP readings with their primary care physicians or nurse practitioners at scheduled visits. Limitations: Potential limitations of this study include the relatively short duration of follow-up, possible technological pitfalls, and need for patients to own a smartphone and have access to the internet to participate. Conclusions: As this study will focus on a high-risk population that has been characterized by a large care gap, it will generate important evidence that would allow targeted and effective population-level strategies to be implemented to improve health outcomes for high-risk hypertensive CKD patients in Canada’s remote communities. Trial Registration: www.clinicaltrials.gov (NCT number: NCT04098354)

Background: Hypertension is a major cause of cardiovascular disease, chronic kidney disease (CKD), and death. Several studies have demonstrated the efficacy of home blood pressure telemonitoring (HBPT) for blood pressure (BP) control and outcomes, but the effects of this intervention remain unclear in patients with CKD. Objective: To determine the impact of HBPT on cardiovascular–related and kidney disease–related outcomes in patients with CKD. Design: Systematic review and meta-analysis. Setting: All studies that met our criteria regardless of country of origin. Participants: Patients with chronic kidney disease included in studies using HBPT for BP assessment and control. Measurements: Descriptive and quantitative analysis of our primary and secondary outcomes. Methods: We searched MEDLINE, Embase, CINAHL Plus, PsycINFO, Cochrane CENTRAL, Web of Science, and gray literature from inception for observational and randomized controlled studies in nondialysis (ND) CKD using HBPT for BP control. We selected studies that used HBPT as intervention (with or without a control arm) for BP control in ND-CKD populations. The primary outcome was change in mean systolic BP (SBP) and mean diastolic BP (DBP). Results: We selected 7 studies from 1669 articles that were initially identified. Overall, pooled estimates in the mean difference (MD) for SBP and DBP were −8.8 mm Hg; 95% confidence interval (CI): −16.2 to −1.4; P = .02 and −2.4 mm Hg; 95% CI: −3.8 to −1.0; P < .001, respectively. For studies comparing intervention with usual care (UC), pooled estimate in MD for SBP was −8.0 mm Hg ( P = .02) with no significant reduction for DBP (−2.6 mm Hg; P = .18). In studies without a UC arm, both SBP and DBP were not significantly reduced ( P > .05). The pooled estimate in MD for estimated glomerular filtration rate showed a significant improvement (5.4 mL/min/1.73 m2; P < .001). Limitations: Heterogeneity and few available studies for inclusion limited our ability to identify a robust link between HBPT use and BP and kidney function improvement. Conclusion: Home blood pressure telemonitoring is associated with mild lowering of BP and moderately improved kidney function in patients with CKD. However, larger studies with improved designs and prolonged interventions are still needed to assess the effects of HBPT on patients’ outcomes. PROSPERO registration ID CRD42020190705

Background and ObjectiveIncreased renal venous pressure (RVP) is common in combined heart and kidney failure. We previously showed that acute RVP elevation depresses renal blood flow (RBF), glomerular filtration rate (GFR), and induces renal vasoconstriction in the absence of changes in blood pressure in healthy rats. We used our established rodent model of chronic combined heart and kidney failure (H/KF) to test whether RVP elevation would impair cardiovascular stability, renal perfusion and exacerbate renal dysfunction.MethodsMale rats were subjected to 5/6 nephrectomy (SNx or Sham) and 6% high salt diet followed 7 weeks later by ligation of the left anterior descending coronary artery (CL or Sham). Experimental groups: CL + SNx (n = 12), Sham CL + SNx (n = 9), CL+ Sham SNx (n = 6), and Sham Control (n = 6). Six weeks later, anesthetized rats were subjected to an acute experiment whereupon mean arterial pressure (MAP), heart rate (HR), RVP, RBF, and GFR were measured at baseline and during elevation of RVP to 20–25 mmHg for 120 min.ResultsBaseline MAP, HR, RBF, and renal vascular conductance (RVC) were comparable among groups. Baseline GFR was significantly depressed in CL + SNx and Sham CL + SNx groups compared to Sham Control and CL + Sham SNx groups. Upon RVP increase, MAP and HR fell in all groups. Increased RVP exacerbated the reduction in RBF in CL + SNx (−6.4 ± 0.9 ml/min) compared to Sham Control (−3.7 ± 0.9 ml/min, p < 0.05) with intermediate responses in Sham CL + SNx (−6.8 ± 1.3 ml/min) and CL + Sham SNx (−5.1 ± 0.4 ml/min) groups. RVP increase virtually eliminated GFR in CL + SNx (−99 ± 1%), Sham CL + SNx (−95 ± 5%), and CL + Sham SNx (−100%) groups compared to Sham Control (−84 ± 15% from baseline; p < 0.05). Renal vascular conductance dropped significantly upon RVP increase in rats with HF (CL + SNx: −0.035 ± 0.011; CL + Sham SNx: −0.050 ± 0.005 ml/min·mmHg−1, p < 0.05) but not Sham CL + SNx (−0.001 ± 0.019 ml/min·mmHg−1) or Control (−0.033 ± mL/min·mmHg−1).ConclusionChronic combined heart and kidney failure primarily impairs renal hemodynamic stability in response to elevated RVP compared to healthy rats.

Introduction Indigenous people represent approximately 5% of the world's population. However, they often have a disproportionately higher burden of cardiovascular disease (CVD) risk and chronic kidney disease (CKD) than their equivalent general population. Several non-pharmacological interventions (e.g., educational) have been used to reduce CVD and kidney disease risk factors in Indigenous groups. The aim of this paper is to describe the protocol for a scoping review that will assess the impact of non-pharmacological interventions carried out in Indigenous and remote dwelling populations to reduce CVD risk factors and CKD. Materials and methods This scoping review will be guided by the methodological framework for conducting scoping studies developed by Arksey and O'Malley. Both empirical (Medline, Embase, Cochrane Library, CINAHL, ISI Web of Science and PsycINFO) and grey literature references will be assessed if they focused on interventions targeted at reducing CVD or CKD among Indigenous groups. Two reviewers will independently screen references in consecutive stages of title/abstract screening and then full-text screening. Impact of interventions used will be assessed using the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework. A descriptive overview, tabular summaries, and content analysis will be carried out on the extracted data. Ethics and dissemination This review will collect and analyse evidence on the impact of interventions of research carried out to reduce CVD and CKD among Indigenous populations. Such evidence will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations, and a report. Also, we will disseminate our findings to the government and Indigenous leaders. Ethical approval will not be required for this scoping review as the data used will be extracted from already published studies with publicly accessible data.

INTRODUCTION:Chronic kidney disease (CKD) is a global-health problem. A significant proportion of referrals to nephrologists for CKD management are early and guideline-discordant, which may lead to an excess number of referrals and increased wait-times. Various initiatives have been tested to increase the proportion of guideline-concordant referrals and decrease wait times. This paper describes the protocol for a systematic review to study the impacts of quality improvement initiatives aimed at decreasing the number of non-guideline concordant referrals, increasing the number of guideline-concordant referrals and decreasing wait times for patients to access a nephrologist.METHODS AND ANALYSIS:We developed this protocol by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (2015). We will search the following empirical electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO and grey literature for studies designed to improve guideline-concordant referrals or to reduce unnecessary referrals of patients with CKD from primary care to nephrology. Our search will include all studies published from database inception to April 2021 with no language restrictions. The studies will be limited to referrals for adult patients to nephrologists. Referrals of patients with CKD from non-nephrology specialists (eg, general internal medicine) will be excluded.ETHICS AND DISSEMINATION:Ethics approval will not be required, as we will analyse data from studies that have already been published and are publicly accessible. We will share our findings using traditional approaches, including scientific presentations, open access peer-reviewed platforms, and appropriate government and public health agencies.PROSPERO REGISTRATION NUMBER:CRD42021247756.