Improvement In Glomerular Filtration Rate Research Articles

Dissociation of Hypertension and Renal Damage After Cessation of High-Salt Diet in Dahl Rats.

Every year, thousands of patients with hypertension reduce salt consumption in the efforts to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure. Dahl salt-sensitive rat model was used for chronic, continuous observation of blood pressure. Rats were fed a high salt diet to induce hypertension, and then the diet was switched back to normal sodium content. We found that developed hypertension was irreversible by salt cessation: after a short period of reduction, blood pressure grew even higher than in the high-salt phase. Notably, the self-sustaining phase of hypertension was sensitive to benzamil treatment due to sustaining epithelial sodium channel hyperactivity, as shown with patch-clamp analysis. Glomerular damage and proteinuria were also irreversible. In contrast, some mechanisms, contributing to the development of salt-sensitive hypertension, normalized after salt restriction. Thus, flow cytometry demonstrated that dietary salt reduction in hypertensive animals decreased the number of total CD45+, CD3+CD4+, and CD3+CD8+ cells in renal tissues. Also, we found tubular recovery and improvement of glomerular filtration rate in the postsalt period versus a high-salt diet. Based on earlier publications and current data, poor response to salt restriction is due to the differential contribution of the factors recognized in the developmental phase of hypertension. We suggest that proteinuria or electrolyte transport can be prioritized over therapeutic targets of inflammatory response.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RIs for males were: 18-79 years, 55.53-92.50 μmol/L;≥80 years, 54.41-96.43 μmol/L. RIs for females were: 18-59 years, 40.42-69.73 μmol/L; 60-79 years, 41.16-73.69 μmol/L;≥80 years, 46.50-73.20 μmol/L. Q-values were set at 73.82 μmol/L (0.84 mg/dL) for males and 53.80 μmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT.

Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT). This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months. Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms. Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.

Chemoradiotherapy treatment with gemcitabine improves renal function in locally advanced cervical cancer patients with renal dysfunction

BackgroundCervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. MethodsThis retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. Results351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). ConclusionCCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.

Long-term outcomes of transcatheter tricuspid valve repair in prohibitive risk patients: futility or benefit?

Abstract Background Transcatheter tricuspid valve repair (TTVR) for tricuspid regurgitation (TR) is an emerging treatment option in inoperable patients. However, patient selection is challenging, and mostly predetermined by comorbidities and non-specific surgical risk scores. Current guidelines (1) distinguish between high-risk (HR) and prohibitive risk (PR) patients, in order to avoid clinical and procedural futility. Therefore, the aim of this study was to understand if PR patients can benefit from TTVR long-term. Methods Forty-one consecutive patients with severe TR were assessed by the heart team, considered inoperable, and underwent edge-to-edge TTVR at our institution between November 2020 and January 2022. They were divided into a PR (n=23) and an HR group (n=18), in accordance with the latest guidelines (1). Subgroup allocation took into account STS (Society of Thoracic Surgeons) risk score, and several comorbidities (Figure 1A). Mean age was 82.2±5.9 (PR) vs 81.1±3.5 years (HR), with mean STS-Score 14.3±6.7% vs 6.2±1.6% (Figure 1B). Results The primary efficacy endpoint of at least one-grade TR reduction by 30 days was recorded in 92.7% of all patients, with no device related complications. By 12 months, 6 patients died, 5 PR and 1 HR, and MACE rate was 18.1%. Secondary endpoints addressed symptoms, quality of life and multiorgan function, which improved in both groups (Figure 2). More precisely, at inclusion, all patients in the PR group were in NYHA class III and IV, while after 12 months only 27.7%. In comparison, there were no more HR patients in NYHA stage III and IV, after one year. Similarly, self-reported quality of life increased, as assessed by the "Kansas City Cardiomyopathy Questionnaire" (KCCQ) score, which increased by 23±18.2 (p&amp;lt;0.001) in PR and 27.5±16.1 (p&amp;lt;0.001) points in HR patients, respectively. Walk distance in the 6-minute test also improved by 79.2±82 (p&amp;lt;0.001) vs 113.6±72.8 (p&amp;lt;0.001) meters. Renal and liver function were also impacted by TR reduction, with statistical significance in the PR group [GFR- Glomerular Filtration Rate improvement from 46.7±13.9ml/min/1,73m2 to 51.9±18.1 (p=0.045) vs 62.1±17.1 to 62.1±18.5 (p=0.990); AST- Aspartate Aminotransferase from 33.7±15.4U/L to 27.3±12.3 (p=0.001) vs 33.2±26.1 to 26.2±6.8 (p=0.188)]. Furthermore, TR reduction led to long-term reverse cardiac remodeling, as right ventricular systolic function increased [TAPSE from 14.2±3.1mm to 17.7±2.2 (p&amp;lt;0.001) vs 16.4±3.5 to 20.7±5.4 (p&amp;lt;0.001)], and right atrial size decreased [indexed volume from 93.5±39.1 ml/m2 to 66.3±42.6 (p=0.005) vs 86.3±57.8 to 63.3±59.5 (p=0.032)]. Conclusions TTVR is feasible in very sick symptomatic patients and is associated with improved quality of life, functional capacity, multiorgan function and reverse cardiac remodeling. Patient selection based on risk assessment with surgical risk scores may deprive many symptomatic inoperable patients of this specific percutaneous treatment.Figure 1Figure 2

Abstract 108: Rejuvenation Potential Of Extracellular Vesicles From Renal Distal Tubular Cells - A Promising Strategy To Prevent Aging-associated Hypertension And Renal Function Impairment

Ageing is characterized by progressive multi-organ functional decline and disrupted homeostasis adaptation. Hypertension and kidney damage become increasingly prevalent as individuals age. Given its high metabolic activity and constant exposure to reactive oxygen species, the kidney is particularly susceptible to age-related deterioration. In our study, aged mice exhibited a notable decline in glomerular filtration rate (GFR) and urinary excretion of sodium, potassium, and calcium, alongside elevated urinary creatinine levels, indicating impaired renal function associated with ageing. Histologically, aged kidneys showed glomerular collapse, thickening of the glomerular basement membrane, and increased glomerular sclerosis. Cellular senescence plays a critical role in renal ageing. Senescent cells display an array of changes in gene and protein expression and thus also altered the contents packaged into extracellular vesicles (EVs), secreted into the extracellular milieu. The protein and RNA composition of EVs varied depending on the age and pathological status of the originating parent cells. Our data showed an increased expression of EV biogenesis protein HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) in aged DCT cells (aDCTs). Consistently, with an increase in EV secretion in aDCTs. Administration of young DCT (yDCT)-derived EVs into aged kidneys resulted in a significant improvement of GFR and urinary ion excretion, accompanied by a reduction in age-associated elevation of systolic blood pressure (SBP). Conversely, when administering aDCT-derived EVs to young mice, we saw a significant decrease in GFR and an increase in SBP, indicating a detrimental effect of aDCT-EVs. Proteomic analysis revealed distinct protein expression profiles between yDCT-EVs and aDCT-EVs. These differentially expressed proteins are highly enriched in ageing regulatory pathways, underscoring the crucial role of DCT-EVs in kidney rejuvenation. Intriguingly, we identified a subset of proteins exclusively present in either yDCT-EVs or aDCT-EVs. Our future research will focus on identifying the key components of DCT-EVs responsible for driving kidney rejuvenation.

#6189 PRECLINICAL VALIDATION OF REPURPOSABLE CANDIDATE DRUG COMPOUNDS FOR CYSTIC NEPHROPATHIES

Abstract Background and Aims Early-onset cystic kidney disease is a clinically and genetically heterogeneous and overlapping group of rare and often severe disorders with limited, mostly symptomatic treatment options. We developed and utilized inherited polycystic cystic kidney disease (PKD) models to search for pharmacological agents that can rescue or mitigate the disease phenotype. Method A high-content screening platform for identification of chemical modifiers of cyst formation and progression in a zebrafish genetic cystic nephropathy model (IFT172 Morpholino-based knockdown in Tg(wt1b:eGFP)), using robotic microscopy with automated image classification and phenotype quantification was used to screen 1280 compounds from the Prestwick library for their cyst-inhibiting activity. Compounds with cyst-inhibitory efficacy and low toxicity in the Zebrafish and oral and trans-placental availability were selected for further study in two rodent PKD models, i.e. PCK and PKD/Mhm (cy/+) rats. Groups of 3-week-old homozygous PCK and heterozygous PKD/Mhm rats were administered orally for 10 weeks three candidate compounds, which included an antihistamine, an anthelmintic and an antifungal agent, or regular ROD16 chow (sick controls). In experimental week 5, blood was taken, and the kidneys were imaged sonographically under anaesthesia. In the last experimental week, glomerular filtration rate was determined by transcutaneous FITC-sinistrin injection. Masson trichrome staining was used to evaluate cyst formation in kidneys. Results 60 compounds with cyst preventive or cyst size reducing activity were identified in the zebrafish screening model. While one third of these compounds caused severe general toxicity, 12 of them showed medium and 4 strong cyst-inhibitory activity with no or mild off-target effects. These substances were from anthelminthic, antihistamine, antifungal and proton pump inhibitor drug classes. Preliminary results in the rodent models suggest that anthelminthic treatment reduced the number of cysts in female (3.3±1.3 vs. untreated control, 5.4±0.9) but not male PCK rats (3.7±0.6 vs. 3.9±0.7) after 10 weeks of treatment. These changes were accompanied by improved glomerular filtration rate (GFR) in treated females (t½: 0.22±0.04 min vs. 0.3±0 min). An improvement in GFR was also observed in female PKD/Mhm rats after 10 weeks of treatment with the anthelmintic compound compared to untreated control animals (t½: 0.24±0.06 vs. 0.51±0.16 min, p = 0.02). Conclusion Candidate cyst-inhibitory drugs identified in a zebrafish model were applied in rat models of PKD. The administration of an anthelmintic agent had a positive impact on the progression of polycystic kidney disease. The beneficial effect appears to be sex specific. If further corroborated, our findings may allow repurposing of a drug approved for another indication to slow disease progression in patients with cystic kidney diseases.

Influence of donor complement component allotype on renal transplantation outcome

Background Improvements in clinical care and immunosuppressive medications have provided positive outcomes following kidney transplantation such as reducing acute rejection rates. Activation of the complement cascade is inevitable in kidney transplantation because of both the specific and nonspecific immunologic responses of the recipient. This study provides insights on the influence of the donor C3 allotype on renal transplant outcome (graft function). Patients and methods The present study was conducted on 50 pairs of donors and recipients of renal transplantation who fulfilled the inclusion and exclusion criteria. C3 allotypes of donor–recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient. The four genotypic groups were analyzed for association with graft function and assessed by serum creatinine, blood urea, and glomerular filtration rate. Results There was a positive statistically significant difference for the group FF/FS donor into SS recipient in comparison with other genotype groups of C3 among recipients, as shown by improvement in glomerular filtration rate, serum creatinine, and blood urea. Conclusion The presence of C3 (F) allele either homozygous or heterozygous in the donor and the absence of this allele in the recipient give a better renal allograft function.

Outcome of Dismembered Pyeloplasty in Children with Unilateral Pelviureteric Junction Obstruction: A Retrospective Observational Study

Introduction: Anderson-Hynes (AH) dismembered pyeloplasty is the standard procedure performed for the management of Pelviureteric Junction Obstruction (PUJO). Ultrasonography (USG) and diuretic renography are of great importance for the diagnosis and follow-up of PUJO. Aim: To evaluate the morphological and functional outcomes of open dismembered pyeloplasty in children with unilateral PUJO and to find the correlation between functional and morphological outcomes. Materials and Methods: A retrospective observational study was conducted, assessing the clinical charts of 200 children under 10 years of age with congenital PUJO who underwent open AH dismembered pyeloplasty in the Department of Paediatric Surgery at a teritary teaching Institute, Government medical college, Thiruvananthapuram, Kerala, India from from June 2015 to June 2020. The preoperative radiological assessment included renal USG and diuretic renography for all patients. Morphological and functional surgical outcomes were measured one year after surgery. The morphologic parameters analysed were the Anteroposterior Diameter (APD) of the pelvis and Parenchymal Thickness (PT). The functional outcome was assessed by improvements in Glomerular Filtration Rate (GFR), Split Renal Function (SRF), and drainage curve. Success was defined as improvement in function and morphology in followup USG and renogram after one year of surgery. Paired t-test was applied for statistical analysis using Statistical Package for the Social Sciences (SPSS) software version 23.0. Results: Among the total 200 patients,180 (90%) cases demonstrated improved renal function after pyeloplasty. Among the total 200 cases, males were 120 (60%) and females were 80 (40%). Morphologic outcome improved in 188 out of 200 (94%) cases. The overall outcome was good in 168 out of 200 (84%) patients. The results showed a moderate negative correlation for APD with respect to SRF (r=-0.677, p-value=0.01) and GFR (r=- 0.430, p-value=0.01), whereas a moderate positive correlation was observed between SRF and GFR (r=0.423, p-value=0.01). Conclusion: AH dismembered pyeloplasty is an effective treatment for PUJO in children, not only relieving obstruction but also improving renal function. The present study recommends considering both morphologic and functional parameters to assess the success of the surgery.

Revisiting Vertical Flap Pyeloplasty in Pelviureteric Junction Obstruction: A Case Series

Pelviureteric Junction Obstruction (PUJO) can cause recurrent Urinary Tract Infections (UTIs), pain, and loss of renal unit function. Surgical intervention is often required, and numerous treatment strategies have been employed. Vertical flap pyeloplasty was initially described as the technique of choice in PUJO patients with the large box-shaped extra-renal pelvis and longer segment strictures (usually &gt;2 cm). In the present case series, 11 patients underwent vertical flap pyeloplasty for PUJO with a large extrarenal box-shaped pelvis. Demographic, perioperative, and follow-up data were recorded. Success was defined as symptomatic improvement and an improvement in early Diethylenetriamine Pentaacetate (DTPA) renogram at six months. In the present series, all 11 patients showed an improvement in Glomerular Filtration Rate (GFR) with an average improvement of 11.9 mL. The procedure was technically easier, less time-consuming, and produced acceptable results. Vertical flap pyeloplasty could be considered as a practical, technically easier, and effective treatment option in PUJO with a large extrarenal pelvis and long segment strictures.

Endocrine disorders in chronic kidney disease

The increasing prevalence of chronic kidney disease gives rise to many diagnostic challenges in the daily care of this group of patients. This paper presents the most clinically significant endocrine disorders accompanying chronic kidney disease, their aetiology, diagnosis, clinical picture and treatment. Endocrine disorders may occur in patients with chronic kidney disease with greater or equal frequency as in the general population. The most important endocrine disorders include: low triiodothyronine syndrome, subclinical and overt hypothyroidism, hypercortisolaemia, hyperprolactinaemia, increased levels of growth hormone, hyperinsulinaemia, insulin resistance and hypogonadism. Hyperthyroidism and autoimmune thyroid disease occur with the same frequency in patients with chronic kidney disease as in the general population. Chronic kidney disease also affects commonly used hormone determinations. The choice of the therapeutic method in patients with chronic kidney disease is not without importance for endocrine disorders. Among patients undergoing dialysis therapy, a temporary increase in free thyroid hormones, a decrease in the severity of hypercortisolaemia and a decrease in hormone levels were observed. Dialysis therapy does not normalise prolactin levels, unlike kidney transplantation, where an improvement in glomerular filtration rate results in the normalisation of serum prolactin. The therapeutic management of some of the presented endocrine disorders is not based on a causal effect, but mainly on controlling their complications (e.g. secondary to hypercortisolaemia – hypertension, diabetes, osteopenia or abdominal obesity). In the remaining cases, hormone replacement therapy was associated with a beneficial effect for the patient: testosterone replacement in obese men with hypogonadism led to a decrease in body mass index, and cyclical transdermal hormone replacement therapy in women with oestrogen deficiency secondary to renal failure inhibited bone demineralisation and thus prevented early osteoporosis.

Longitudinal GFR trends after neoadjuvant chemotherapy prior to nephroureterectomy for upper tract urothelial carcinoma.

Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU). Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort. One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 m2 from the beginning of chemotherapy to 1-year post-surgery. In patients receiving cisplatin, a mean decline of 26.2 ml/min/1.73 m2 was observed vs. 8.8 ml/min/1.73 m2 without cisplatin-based NAC (P < 0.01). GFR after RNU was unchanged between 3 and 12 months postoperatively. At 1 to 3 months after RNU, 19% of patients had GFR<30 ml/min/1.73m2. Improvement in GFR during NAC was associated with invasive final pathologic stage (P = 0.018) and worse overall survival (P = 0.049). In patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation.

Low-Dose Dopamine in the Management of Intradialysis Hypotension: A Retrospective Cohort Study in Nigeria

Introduction: Intradialytic hypotension (IDH) still remains a common finding in maintenance haemodialysis despite improvements in dialysis delivery. Measures are needed to minimise some aftermath of IDH like dialysis termination, which can impact poorly on dialysis outcome. Methods: This retrospective study assessed IDH in a low-income setting, and compared two cohorts of IDH with and without dopamine treatment. Results: Of the 416 participants, 92 (22.1%) had at least an episode of symptomatic IDH. Of these, 20 (21.7%) were treated with dopamine. Of the 2,205 sessions, 468 (21.2%) had symptomatic IDH, of which 63 (13.4%) with severe IDH were treated with dopamine. The mean age of all participants and dopamine treatment participants were 50.8 ± 9.3 years and 64.6 ± 9.5 years, respectively (P=0.001). Blood pressure (BP) reductions following dialysis were more with females (P=0.04). Dialysis dose was adequate in 7.9% and 4.2% of sessions with and without dopamine (P&lt;0.001). Improvements in glomerular filtration rate were greater in dopamine-treated sessions (P=0.03 and P=0.04, respectively). Fewer anti-hypertensives (aOR: 14.64; 95% confidence interval [CI]: 7.88–20.41), low predialysis systolic (aOR:5.59; 95% CI: 3.88–9.41), and diastolic blood pressure (aOR: 5.78; 95% CI: 4.06-9.81) were independently associated with dopamine-treated sessions. Conclusion: IDH was found in 21.2% of dialysis sessions. 13.4% with severe IDH had dopamine treatment. Participants with dopamine-treated sessions had fewer dialysis terminations and hospitalisations, and dopamine treatment improved the prescribed dialysis and gave higher dialysis doses. Considering the economic effects of dialysis termination in low-income nations, intradialytic dopamine could be very beneficial.

Montelukast as an Add-on Drug in Induced Azotemia in Humans Following Gastroenteritis

Background: Gastroenteritis, as a rare and heterogeneous condition, is characterized by patchy or diffuse infiltration of gastrointestinal tissue. Induced azotemia in humans following gastroenteritis has been evaluated in some studies. Objectives: The aim of present study was to evaluate the effect of montelukast on induced azotemia in humans following gastroenteritis. Methods: This study examined children with gastroenteritis with moderate dehydration and more than 3 years of age. The cases had a glomerular filtration rate (GFR) less than 90 and were evaluated in two groups of control (n = 20) and intervention (n = 20). Montelukast (5-mg tablets) was given to patients in the intervention group for 5 days. Normal saline at a rate of 20 cc/kg was given to both groups within 20 minutes until clinical symptoms improved. Finally, the improvement of renal function was evaluated and compared between the 2 groups using SPSS. Results: Out of 40 evaluated patients, the mean age of the control and intervention groups was 5.52 and 5.15 years, respectively. Also, 13 cases (65.0%) in the control group and 9 cases (45.0%) in the control group were males. The mean creatinine (Cr) was significantly reduced after treatment in the intervention group (P = 0.001). Also, the mean GFR after treatment was significantly higher in the intervention group (P = 0.001), and GFR improvement duration was significantly lower in the intervention group (P = 0.002). Conclusions: Montelukast as an add-on drug was effective in reducing the time of GFR enhancement; thus, we can consider it as an add-on drug in azotemia.

Prognostic impact of renal function trajectories in patients with STEMI and kidney dysfunction undergoing primary percutaneous coronary intervention: An analysis of ten years all-comers registry

BackgroundRenal dysfunction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) indicates a poor long-term prognosis. However, the prognostic value of the improvement or stabilisation of renal function during follow-up has not yet been assessed. This study aimed to investigate the long-term predictive impact of the improvement or stabilisation of renal function after one year of follow-up in patients with STEMI undergoing pPCI with renal dysfunction at discharge. MethodsThis prospective, single-centre cohort study included 2170 consecutive patients with STEMI who underwent pPCI. The glomerular filtration rate (GFR) was determined at hospital discharge and one-year follow-up. The median clinical follow-up was 72 months. ResultsAmong the 2004 patients, 393 (19.6%) had a GFR <60 ml/min, and 1611 (80.4%) had a GFR ≥ 60 ml/min at discharge. Among patients with GFR <60 ml/min, data at one-year follow-up were available for 342. Of these patients, 127 (32%) showed improvement in renal function (defined as improvement in the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification), 47 (12%) showed worsening of renal function (defined as worsening of the KDIGO CKD classification), and 168 (43%) showed no category changes. Improvement or stabilisation of GFR at one year of follow-up was associated with a reduction of major adverse cardiovascular events (MACE) [HR 0.51, 95% CI: 0.35–0.75, p = 0.001] and all-cause mortality [HR 0.54, 95% CI: 0.34–0.84, p = 0.007] during follow-up. ConclusionsThe improvement or stabilisation of renal function at one-year follow-up in patients with STEMI and renal dysfunction is associated with a better long-term prognosis.

Current kidney function parameters overestimate kidney tissue repair in reversible experimental kidney disease

Although underlying mechanisms and the clinical course of kidney disease progression are well described, less is known about potential disease reversibility. Therefore, to analyze kidney recovery, we adapted a commonly used murine chronic kidney disease (CKD) model of 2,8- dihydroxyadenine (2,8-DHA) crystal-induced nephropathy to study disease recovery and efficacy of disease-modifying interventions. The recovery phase after CKD was characterized by improved kidney function after two weeks which remained stable thereafter. By contrast, even after eight weeks recovery, tubular injury and inflammation were only partially reduced, and fibrosis persisted. Deep-learning-based histologic analysis of 8,604 glomeruli and 596,614 tubular cross sections revealed numerous tubules had undergone either prominent dilation or complete atrophy, leading to atubular glomeruli and irreversible nephron loss. We confirmed these findings in a second CKD model, reversible unilateral ureteral obstruction, in which a rapid improvement of glomerular filtration rate during recovery also did not reflect the permanent histologic kidney injury. In 2,8-DHA nephropathy, increased drinking volume was highly effective in disease prevention. However, in therapeutic approaches, high fluid intake was only effective in moderate but not severe CKD and established tissue injury was again poorly reflective of kidney function parameters. The injury was particularly localized in the medulla, which is often not analyzed. Thus, recovery after crystal- or obstruction-induced CKD is characterized by ongoing tissue injury, fibrosis, and nephron loss, but not reflected by standard measures of kidney function. Hence, our data might aid in designing kidney recovery studies and suggest the need for biomarkers specifically monitoring intra-kidney tissue injury.

Effects of bariatric surgery on renal function and associated factors with bivariate analysis: a cohort study

Background: Obesity is a global pandemic, caused by genetic, biological and social factors, increasing the risk of many chronic diseases, including kidney disease. Bariatric surgery can control associated comorbidities and also improve renal function. Thus, the aim of this study was to evaluate the effect of bariatric surgery on renal function and associated factors, through bivariate analysis. Methods: A cohort, prospective, analytical study was carried out in the Department of surgery and obesity, in Campina Grande - Paraíba, Brazil. Thirty-five obese patients were evaluated in the preoperative period of bariatric surgery and after one year of bariatric surgery. Sociodemographic and anthropometric data were collected, body mass index was calculated, and renal function was estimated through the glomerular filtration rate. Results: Predominantly female (71.4%) and white (77.1%) patients were observed. Regarding the type of bariatric surgery, most patients (65.7%) underwent the sleeve technique. There was no significant difference between the mean levels of cystatin C pre and post bariatric surgery. There was a significant improvement in the mean glomerular filtration rates in the postoperative period (p=0.09). In further analysis of the association between the variables: type of bariatric surgery, diabetes or hypertension outcomes, no association was observed with the outcome improvement in glomerular filtration rate, without statistical significance, respectively (p = 0.312; p =0.217; p = 0.476). Similarly, there was no statistically significant difference between the variable loss of body mass index, under the effect of bariatric surgery, in relation to the outcome of the glomerular filtration rate (p = 0.904). Conclusion: After analyzing the association between outcome of glomerular filtration rate and the studied variables, no association was observed between these variables, under the effect of bariatric surgery, with improvement in glomerular filtration rate. Thus, bariatric surgery is associated with improvement of renal function independently.

Arteriovenous fistula in predialysis chronic kidney disease patients and rate of decline of glomerular filtration rate.

To quantify the evidence for the role of arteriovenous fistula (AVF) in predialysis CKD patients for the rate of decline of glomerular filtration rate (GFR). Pre-emptive placement of arteriovenous fistula (AVF) in late-stage chronic kidney disease (CKD) patients is being advocated by all the major guidelines. Recent studies have suggested that pre-emptive AVF has a beneficial effect on glomerular filtration rate (GFR) also. We conducted a literature search to retrieve all published studies related to the effect of AVF on the rate of decline of GFR using the electronic databases Google Scholar, PubMed, Central, Cochrane Library, clinialtrial.gov. Screening of studies and data extraction were done according to the PRISMA guidelines. We used the NIH assessment tool for the methodological quality assessment of the included studies. Extracted data from the six studies were pooled and analyzed. Six studies involving 3871 patients reported the effect of AVF creation on the rate of decline of GFR in late CKD patients. Evidence for statistically significant decline of eGFR after AVF creation compared to prior status (SMD -1.57, 95% CI -3.08 to -0.07, p < 0.001) was observed. Our meta-analysis observed preliminary evidence that the creation of AVF might have a potential added benefit in terms of estimated GFR improvement, though to a very small extent with a low level of certainty. More scientific data with high-quality studies are needed to substantiate this finding.

Renoprotective opportunities of Lespedeza capitata in patients with chronic kidney disease and type 2 diabetes mellitus

Background. Today, issues of renoprotection have gone beyond the use of antihypertensive therapy alone. Stable glucose-lowering and urate-lowering therapy are integral parts of modern renoprotection, which improve the functional state of the kidneys by increasing the glomerular filtration rate (GFR) and reducing the albumin excretion rate (AER) and the albumin-to-creatinine ratio (ACR). Nevertheless, hypoazotemic therapy aimed at reducing the content of nitrogenous wastes remains the leading component of the treatment of patients with chronic kidney disease (CKD). The aim of the study is the assessment of the renoprotective potential of the drug Libera (Lespedeza capitata) in patients with CKD stages 2–3 on the background of type 2 diabetes mellitus (DM). Materials and methods. The study included 107 patients with type 2 DM, aged 19 to 75 years (female— 41.1%, male — 58.9%), CKD stages 2–3, micro- and macroalbuminuria (category A2 and A3). The patients were divided into two groups: group I — traditional stable glucose-lowering and antihypertensive therapy (n = 50) and group II — traditional stable glucose-lowering and antihypertensive therapy in combination with Libera (Lespedeza capitata) (n = 57), which was prescribed 1 capsule t.i.d. regardless of food intake for 3 months. The criteria for the effectiveness of treatment were dynamics of GFR, AER/ACR in daily urine. The observation period for the patients was 3 months. Results. The renoprotective potential of Lespedeza capitata (Libera) was demonstrated after 3 months of treatment in the form of a significant increase in GFR in patients with CKD stage 2 in group II up to 79.0 ± 1.4 ml/min/1.73 m2 in comparison with the initial data (p &lt; 0.01) and the results obtained in group I after 3 months of using only traditional stable glucose-lowering and antihypertensive therapy (p &lt; 0.05). The use of Libera in the complex treatment of patients of the II group with CKD stage 3 against the background of type 2 DM for 3 months had a positive effect on nitrogen and water excretory kidney function, which manifested itself in an improvement in GFR to 56.6±2.1ml/min/1.73m2 in comparison with the initial data (p &lt; 0.05) and the results obtained in group I — 50.8 ± 1.9 ml/min/1.73m2 (p&lt;0.05). In group I with traditional stable glucose-lowering and antihypertensive therapy, only 3 patients (9.1%) transferred from category A2 to category A1 (normoalbuminuria) after 3 months and 2 patients (11.8%) from category A3 to category A2. In group II, the appointment of Lespedeza capitata (Libera) in combination with stable glucose-lowering and antihypertensive therapy facilitated the transfer of 10 patients (27.8%) from category A2 to A1 and 7 patients (33.3%) from category A3 to A2 (p &lt; 0.001). Conclusions. Lespedeza capitata (Libera) in combination with traditional stable glucose-lowering and antihypertensive therapy contributes to the preservation and improvement of the filtration function of the kidneys, a decrease in AER/ACR in patients with CKD stage 2–3 (3a і 3b) against the background of type 2 DM and proves renoprotective efficiency and safety.

Efficacy and safety of bortezomib in the treatment of active antibody-mediated rejection in adult kidney-transplant recipients: A single-center retrospective study

Introduction: The management of active antibody-mediated rejection (ABMR) is evolving, and optimal treatment remains uncertain due to incomplete understanding of pathogenesis. Bortezomib is found to be useful in the treatment of active ABMR. We studied the efficacy and safety of bortezomib in renal-transplant recipients with active ABMR. Materials and Methods: We retrospectively included renal-transplant recipients with active ABMR, who received bortezomib as main management. Results: Eighteen live-related renal-transplant recipients of active ABMR were included. C4d was positive in 14 patients and negative in eight patients. Patients with active ABMR had a mean improvement in glomerular filtration rate (GFR) of 7, 10.5, and 15 ml/min/1.73 m2 at 3, 6, and 12 months, respectively, from baseline GFR. Improvement was significant at 3 (P = 0.009) and 6 months (P = 0.018) of follow-up. Conclusion: Bortezomib may be a safe and effective therapy in patients with active ABMR in patients.