Lower Serum Creatinine Levels Research Articles

The anti-inflammatory activity of resveratrol in acute kidney injury: a systematic review and meta‐analysis of animal studies

Context Accumulated experimental evidence suggests that resveratrol (RSV) may have an effect on acute kidney injury (AKI) by inhibiting inflammation. However, the credibility of the evidence for this practice is unclear. Objective This study investigated the effect of RSV on AKI and the underlying mechanism. Methods We searched PubMed, EMBASE, and Web of Science from 2005 to April 2022 for controlled animal trials assessing the effect of conventional resveratrol versus placebo on renal function outcome after AKI. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42022329596. Results We retrieved 455 studies, 25 studies comprising data of 436 animals that met the inclusion criteria. Our meta-analysis suggested that RSV treatment was significantly associated with lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The greatest effects were recorded in low-dose (<20 mg/kg/day) groups rather than in high-dose (> 20 mg/kg/day) groups. For time-response effects, subgroup analysis indicated that intervention duration of RSV can influence the treatment effect, and more beneficial effects were observed when studies had a drug administration time of <2 weeks. Discussion and conclusions This systematic review of animal AKI studies showed a consistently favourable effect of RSV as compared to placebo on renal function outcomes that increased with lower TNF-α, IL-6, and IL-1β. RSV has a more beneficial effect on SA-AKI animal models than the others. When the RSV intervention dose was low (< 20 mg/kg/day) and the intervention time was <2 weeks, more benefits could be observed.

Factors Affecting the Outcome of Medical Treatment in Cats with Obstructive Ureteral Stones Treated with Tamsulosin: 70 Cases (2018-2022).

Simple SummaryOther than surgical approaches the treatment options for feline ureterolithiasis are limited compared to those of human medicine. After various studies on ureteral muscle relaxation drugs, tamsulosin has been used as a treatment for distal ureteral stones in human medicine. However, the available clinical veterinary data on the efficacy of drugs that relax the ureter are limited. Thus, this study aimed to investigate the factors affecting the outcome of tamsulosin treatment for feline ureterolithiasis. With tamsulosin treatment, the ureteric stone passage was confirmed in 22 out of 70 cats, with a success rate of 31.43%. Negative factors with statistical significance for stone passage in this study were high baseline creatinine levels, female sex, proximal location of stones, and large diameter stones. The results of this study suggest that tamsulosin can be considered for the treatment of ureterolithiasis in cats with small distal ureteral stones. In addition, this study serves as an important reference for determining whether medical treatment of feline ureteral obstruction using tamsulosin can be attempted.The incidence of diseases associated with feline ureteral obstruction is increasing; however, non-surgical treatment options are limited. This study evaluated the outcome of medical treatment in cats with obstructive ureteral stones treated with tamsulosin and identified potential factors predicting spontaneous stone passage. We retrospectively reviewed 70 client-owned cats treated at the Western Referral Animal Medical Center, Seoul, Korea, from 2018 to 2022. All the cats had obstructive ureterolithiasis and were treated using tamsulosin. The baseline characteristics of the cats, stone diameter and location, and stone passage outcomes were analyzed. Stone passage occurred in 22 cats; the remaining 48 cats showed no change in stone locations. Sex, creatinine, and diameter and location of stones were potential risk factors associated with successful stone passage, but age, weight, and side of the stone were not. No serious adverse events related to tamsulosin treatment were observed. This is the first study to identify the risk factors predictive of the spontaneous stone passage of cats with obstructive ureterolithiasis after tamsulosin treatment. Tamsulosin could be an alternative treatment for ureteral obstruction in male cats with smaller distal ureteral stones and low baseline serum creatinine levels. These findings could help develop guidelines for treating feline ureterolithiasis.

Effect of Hypertonic Saline Solution Combined with Furosemide on Acute Heart Failure: A Meta-Analysis.

Background The efficacy of hypertonic saline solution (HSS) combined with furosemide in treating acute heart failure is controversial. This meta-analysis explores the efficacy of HSS combined with furosemide for the treatment of acute heart failure. Methods Literature were searched from databases, including PubMed, Web of Knowledge, Embase, Central, CMKI, Wanfang, and VIP. The inclusion criteria were as follows: (1) subjects: patients with acute heart failure; (2) the experimental group and the control group were properly set up; (3) intervention measures: patients in the experimental group were treated with HSS + furosemide, and patients in the control group were treated with furosemide; (4) the outcomes included at least one of the following indicators: readmission rate, mortality, 24 h urine volume, weight loss, and serum creatinine; and (5) randomized controlled trial (RCT). The method recommended by Cochrane Collaboration Network was used to evaluate the risk bias. The heterogeneity among the studies was evaluated through the chi-square test, and the publication bias was assessed by the Egger test. The results were described using risk ratio (RR), mean difference (MD), and 95% confidence interval (CI). Results The readmission rate in the HSS + furosemide group was lower than that in the furosemide group (RR = 0.53, 95% CI [0.46, 0.60], P < 0.00001), with no heterogeneity among the literature (P = 0.21, I2 = 29%). Patients in the HSS + furosemide group had a lower mortality rate than that in the furosemide group (RR = 0.55, 95% CI [0.46, 0.65], P < 0.00001). The chi-square test result indicated no heterogeneity among the literature (P = 0.25, I2 = 23%). Furthermore, the 24 h urine volume of patients in the HSS + furosemide group was higher than that in the furosemide group (MD = 497.29, 95% CI [457.61, 536.96], P < 0.00001). There was no heterogeneity among the literature (P = 0.58, I2 = 0%). In contrast, patients in the HSS + furosemide group demonstrated a lower serum creatinine level than those in the furosemide group (MD = −0.45, 95% CI [-0.51, -0.39], P < 0.00001). However, heterogeneity was observed among the literature (P < 0.00001, I2 = 81%). The weight loss in the HSS + furosemide group was higher than that in the furosemide group (MD = 1.83, 95% CI [1.51, 2.15], P < 0.00001). There was no heterogeneity among the literature (P = 0.42, I2 = 2%). Egger test showed no publication bias among the literature (P > 0.05). Conclusion Despite the heterogeneity and bias in our study, the combination of HSS with furosemide is promising in patients with acute heart failure. However, further research is still needed to confirm.

Myeloid expression of the anti-apoptotic protein Mcl1 is required in anti-myeloperoxidase vasculitis but myeloperoxidase inhibition is not protective

Antibodies to neutrophil and monocyte myeloperoxidase and proteinase 3 are a feature of anti-neutrophil cytoplasmic antibody vasculitis, a disease with significant morbidity for which new treatments are needed. Mice with a myeloid-specific deletion of the anti-apoptotic protein Mcl1 have reduced numbers of circulating neutrophils. Here, we assessed if myeloid-specific Mcl1 was required in murine anti-myeloperoxidase vasculitis and whether inhibition of myeloperoxidase was protective. In a murine model of anti-neutrophil cytoplasmic antibody vasculitis, induced by anti-myeloperoxidase antibody, mice with a myeloid-specific deletion of Mcl1 were protected from disease. They had fewer crescents, neutrophils, and macrophages in the glomeruli, lower serum creatinine levels and reduced albuminuria compared with controls. At baseline and day six after disease induction they had fewer circulating neutrophils than controls. At day six there were also fewer circulating monocytes. Myeloperoxidase inhibition with AZD5904 had no effect on histological or biochemical parameters of disease, and there was also no reduction in albuminuria at day one, two, five or seven after disease induction. These findings persisted when disease was induced without granulocyte-colony stimulating factor, which increases disease severity. A second myeloperoxidase inhibitor, AZM198, also showed no evidence of an effect, although both AZD5904 and AZM198 inhibited human neutrophil extracellular trap formation invitro. Thus, our results show that while myeloid-specific Mcl1 is required in this model of anti-myeloperoxidase vasculitis, myeloperoxidase inhibition is not protective.

Blood pressure and kidney function in neonates and young infants with intrauterine growth restriction

BackgroundIntrauterine growth restriction (IUGR) has been associated with changes in kidney anatomy, nephrogenesis and the vascular system, resulting in secondary arterial hypertension and kidney damage in adulthood. Here, we compare routine clinical and metabolic parameters between IUGR and non-IUGR study participants in the neonatal and early infant period.MethodsA total of 39 IUGR and 60 non-IUGR neonates were included during an 18-month study period. We compared blood pressure, serum creatinine (SCr), urea nitrogen (BUN), urinary albumin, α-1-microglobulin, transferrin, immunoglobulin G and total protein excretion in spontaneous urine normalized by urine creatinine level during the hospital stay.ResultsThere were no significant differences in mean values of blood pressure and urinary protein excretion between cases and controls. SCr and BUN levels were lower in the IUGR group compared to the non-IUGR group.ConclusionsThe lower levels of SCr and BUN may be attributed to lower liver and muscle mass in IUGR neonates and young infants. Biomarkers currently used in routine clinical care do not allow early postnatal prediction of higher blood pressure or worse kidney function due to IUGR, so further studies are needed.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Sexual dimorphic response to rituximab treatment: A longitudinal observational study in a large cohort of patients with primary membranous nephropathy and persistent nephrotic syndrome.

Rituximab is one of the first-line therapies for patients with membranous nephropathy (MN) at high risk of progression towards kidney failure. We investigated whether the response to Rituximab was affected by sex and anti-PLA2R antibody levels in 204 consecutive patients (148 males and 56 females) with biopsy-proven MN who were referred to the Nephrology Unit of the Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII from March 2001 to October 2016 and managed conservatively for at least 6 months. The primary outcome was a combined endpoint of complete (proteinuria <0.3 g/24 h) or partial (proteinuria <3.0 g/24 h and >50% reduction vs. baseline) remission. Patients gave written informed consent to Rituximab treatment. The study was internally funded. No pharmaceutical company was involved. Anti-PLA2R antibodies were detectable in 125 patients (61.3%). At multivariable analyses, female gender (p = 0.0198) and lower serum creatinine levels (p = 0.0108) emerged as independent predictors of better outcome (p = 0.0198). The predictive value of proteinuria (p = 0.054) and anti-PLA2R titer (p = 0.0766) was borderline significant. Over a median (IQR) of 24.8 (12.0–36.0) months, 40 females (71.4%) progressed to the combined endpoint compared with 73 males (49.3%). Anti-PLA2R titers at baseline [127.6 (35.7-310.8) vs. 110.1 (39.9–226.7) RU/ml] and after Rituximab treatment were similar between the sexes. However, the event rate was significantly higher in females than in males [HR (95%): 2.12 (1.44–3.12), p = 0.0001]. Forty-five of the 62 patients (72.3%) with anti-PLA2R titer below the median progressed to the combined endpoint versus 35 of the 63 (55.6%) with higher titer [HR (95%): 1.97 (1.26–3.07), p < 0.0029]. The highest probability of progressing to the combined endpoint was observed in females with anti-PLA2R antibody titer below the median (86.7%), followed by females with anti-PLA2R antibody titer above the median (83.3%), males with titer below the median (68.1%), and males with titer above the median (44.4%). This trend was statistically significant (p = 0.0023). Similar findings were observed for complete remission (proteinuria <0.3 g/24 h) and after analysis adjustments for baseline serum creatinine. Thus, despite similar immunological features, females were more resilient to renal injury following Rituximab therapy. These findings will hopefully open new avenues to identify the molecular pathways underlying sex-related nephroprotective effects.

O006 A randomised trial of normothermic machine perfusion versus static cold storage in donation after circulatory death renal transplantation

Abstract Introduction Kidneys from donation after circulatory death (DCD) donors are more susceptible to cold storage (CS) injury and have a high risk of delayed graft function (DGF). This trial is the first to compare normothermic machine perfusion (NMP) to conventional CS in DCD kidney transplantation. Methods In a multicentre randomised control trial, DCD kidneys were randomised to either NMP or CS. NMP kidneys were perfused for 60min with an oxygenated red-cell-based solution (36.0°C) The primary end point was DGF defined as the requirement for dialysis in the first 7days post-transplant. Secondary outcome measures included renal function up to 12 months posttransplant and patient/ graft survival. For all outcome measures a logistic regression model was used adjusted for cold ischaemic time, donor age, left/right kidney and centre. Results February 2016-March 2020, 338 kidneys were randomised into the trial. Twenty-five kidneys did not undergo NMP due to logistical/technical difficulties but were included in an intention-to-treat analysis. Twenty-seven kidneys in the NMP and 21 in the CS group where not transplanted and excluded; 143 NMP and 147 CS kidneys were analysed. There was no significant difference in the rate of DGF (NMP 61% vs CS 58%; P=0.624). Secondary outcome measures demonstrated a significantly higher creatinine reduction ratio day 2(CRR2) (P=0.035) and significantly lower levels of serum creatinine across all timepoints in the NMP group (P=0.024). Conclusion A short end period of NMP did not reduce rates of DGF in DCD kidneys. Secondary outcome measures suggest that NMP may improve renal function. Take-home message This is the first randomised controlled trial of normothermic machine perfusion (NMP) in clinical transplantation. The results suggest that NMP may improve the renal function of DCD kidneys.

Role of Serum Creatinine Levels in Prognostic Risk Stratification of Prostate Cancer Patients.

BackgroundStudies on the relationship between serum creatinine and the prognosis of prostate cancer have been very limited. The aim of this study was to investigate the role of serum creatinine in the prognostic risk stratification of patients with prostate cancer.Material/MethodsWe identified 1134 eligible patients from the “Prostate Cancer Data Set” in the National Clinical Medical Science Data Center. Patients with prostate cancer were divided high- and low-risk prognostic groups according to prostate-specific antigen levels and Gleason scores and were divided into 5 groups according to serum creatinine quintile: Q1 (<70.1 umol/L), Q2 (70.1–76.8 umol/L), Q3 (76.8–83.4 umol/L), Q4 (83.4–92.1 umol/L), and Q5 (>92.1 umol/L). Multivariate logistic regression and a multiple restricted cubic spline method were used to evaluate the relationship between serum creatinine level and the level of prostate cancer prognostic risk.ResultsOf the 1134 patients with prostate cancer, 134 (11.8%) had a high-risk prognosis. Compared with the Q2 group (the reference group), the lowest serum creatinine levels in the Q1 group and the highest serum creatinine levels in groups Q5, Q3, and Q4 were associated with a high-risk prognosis, and this association remained significant after adjusting for confounders. The multiple restricted cubic spline regression model showed the relationship between serum creatinine level and high-risk prognosis was U-shaped.ConclusionsSerum creatinine level was an independent predictor of high-risk prognosis. Controlling serum creatinine levels between 70.1 and 76.8 umol/L in patients with prostatic cancer may benefit the prognosis of patients with prostatic cancer.

Vaccination against connective tissue growth factor attenuates the development of renal fibrosis

There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.

Repeatedly Measured Serum Creatinine and Cognitive Performance in Midlife

Serum creatinine is typically used to assess kidney function. Impaired kidney function and thus high serum creatinine increase the risk of poor cognitive performance. However, serum creatinine might have a nonlinear association because low serum creatinine has been linked to cardiovascular risk and impaired cognitive performance. We studied the longitudinal association between serum creatinine and cognitive performance in midlife. Since 2001, participants from the Cardiovascular Risk in Young Finns Study were followed up for 10 years. Serum creatinine was measured repeatedly in 2001, 2007, and 2011. Sex-specific longitudinal trajectories for serum creatinine among participants without kidney disease were identified with latent class growth mixture modeling. Overall cognitive function and 4 specific domains-working memory, episodic memory and associative learning, reaction time, and information processing-were assessed with a computerized cognitive test. Four serum creatinine trajectory groups with clinically normal serum creatinine were identified for both men (n = 973) and women (n = 1,204). After 10 years of follow-up, cognitive testing was performed for 2,026 participants 34 to 49 years of age (mean age 41.8 years). In men and women, consistently low serum creatinine was associated with poor childhood school performance, low adulthood education, low adulthood annual income, low physical activity, and smoking. Compared to the men in the low serum creatinine trajectory group, those in the high serum creatinine group had better overall cognitive performance (β = 0.353 SD, 95% CI 0.022-0.684) and working memory (β = 0.351 SD, 95% CI 0.034-0.668), while those in the moderate (β = 0.247 SD, 95% CI 0.026-0.468) or normal (β = 0.244 SD, 95% CI 0.008-0.481) serum creatinine groups had better episodic memory and associative learning. No associations were found for women. Our results indicate that in men, compared to low serum creatinine levels, consistently high levels may be associated with better memory and learning function in midlife.

Sarcopenia in Non-Dialysis Chronic Kidney Disease Patients: Prevalence and Associated Factors.

BackgroundSarcopenia is related to morbidity and mortality in non-dialysis Chronic Kidney Disease (ND-CKD) patients; however, the pathophysiology of sarcopenia remains unclear. The study aimed to assess the prevalence and factors associated with sarcopenia in ND-CKD individuals.MethodsWe cross-sectionally evaluated 139 prevalent ND-CKD patients attending our outpatient clinic at Hospital das Clínicas of the Federal University of Pernambuco, between April and October 2019. Patients older than 18 years old and at G3-G5 CKD stages were included. Hand grip strength, Muscle Mass appendicular Index, and Gait Speed (GS) were defined by the standards of the European Working Group on Sarcopenia in Older People 2 guideline.ResultsSarcopenia prevalence was 20.9% and severe sarcopenia 2.9%. Sarcopenic were mostly found in elderly ones (64.8 ± 13.5 years vs. 54.9 ± 12.8 years, p < 0.001), revealing lower body mass index [26.1 (6.8) vs. 28.6 (6.2), p = 0.023], lower phase angle (PhA) [4.50 (1.10) vs. 5.60 (1.20), p < 0.001] and lower GS [1.00 (0.50) vs. 1.40 (0.4), p < 0.001]. They also presented lower serum creatinine levels [2.40 (1.50) vs. 3.0 (1.8), p = 0.032], lower Albumin-to-Creatinine Ratio [72.60 (1008.30) vs. 342.30 (1172.1), p = 0.039] and Hemoglobin levels [11.45 (1.8) vs. 12.60 (2.40), p = 0.003], and higher levels of C-reactive protein [0.2 (0.80) vs. 0.03 (0.3), p = 0.045] compared to non-sarcopenic. Under Poisson Multivariate Model, PhA [Relative precision (RP): 0.364, Confidence Interval (CI) (95%):0.259–0.511, p < 0.001], Interleukin six (IL-6) [RP: 1.006, CI (95%):1.001–1.01, p = 0.02] and serum creatinine levels [RP: 0.788, CI (95%): 0.641–0.969, p = 0.024] were associated with sarcopenia.ConclusionsSarcopenia predominance was identified in our ND-CKD population, and was associated with lower PhA values, higher IL-6 levels, and lower serum creatinine levels.

Therapeutic role of uterine-derived stem cells in acute kidney injury

BackgroundAcute kidney injury (AKI) causes abrupt deterioration in kidney function that disrupts metabolic, electrolyte and fluid homeostasis. Although the prevalence of AKI is steadily increasing, no definitive treatment options are available, leading to severe morbidity and mortality. We evaluated the role of uterine-derived multipotent stem cells in kidney regeneration after ischemic AKI.MethodsFemale C57BL/6J mice were hysterectomized and subsequently subject to AKI by either unilateral or bilateral renal ischemia–reperfusion injury. Uterine-derived cells (UDCs), containing a population of uterine stem cells, were isolated from the uteri of female transgenic DsRed mice and injected intravenously to AKI mice. Engraftment of DsRed cells was analyzed by flow cytometry while serum creatinine levels were determined colorimetrically. Expression of UDC markers and cytokine markers were analyzed by immunohistochemical and qRT-PCR methods, respectively. The Kaplan–Meier method was used to analyze survival time while unpaired t test with Welch’s correction used for data analysis between two groups.ResultsMice with an intact uterus, and hence an endogenous source of UDCs, had a higher survival rate after bilateral ischemic AKI compared to hysterectomized mice. Mice treated with infusion of exogenous UDCs after hysterectomy/AKI had lower serum creatinine levels and higher survival rates compared to controls that did not receive UDCs. Engraftment of labeled UDCs was significantly higher in kidneys of bilateral ischemic AKI mice compared to those that underwent a sham surgery. When unilateral ischemic AKI was induced, higher numbers of UDCs were found in the injured than non-injured kidney. Immunofluorescence staining demonstrated double-positive DsRed/Lotus tetragonolobus agglutinin (LTA) positive cells and DsRed/CD31 positive cells indicating contribution of UDCs in renal tubular and vascular regeneration. Expression of Cxcl12, Bmp2, Bmp4, and Ctnf in renal tissue was significantly higher in the UDCs injection group than the control group.ConclusionsUDCs engrafted injured kidneys, contributed to proximal tubule and vascular regeneration, improved kidney function and increased survival in AKI mice. UDC administration is a promising new therapy for AKI. Endogenous uterine stem cells likely also preserve kidney function, suggesting a novel interaction between the uterus and kidney. We suggest that hysterectomy may have a detrimental effect on response to renal injury.

Efficacy of intravenous hydration during extracorporeal shock wave lithotripsy in improving ureteral stone treatment success rate.

The treatment efficacy of extracorporeal shock wave lithotripsy for urolithiasis depends on several factors. We aimed to evaluate the impact of intravenous hydration during shock wave lithotripsy on stone treatment success rate in patients with ureteral stones. We retrospectively evaluated patients with ureteral stones <2 cm in diameter treated with extracorporeal shock wave lithotripsy at two sites. Patients from one of the sites received intravenous hydration with 500 mL of 0.9% NaCl. Stone treatment success status was defined as stone-free or residual ureteral stones <0.4 cm in diameter 1 month after the procedure. Predictive factors associated with treatment success were evaluated using univariate and multivariate logistic regression. Overall, 146 consecutive patients with ureteral stones were included. Eighty (54.8%) patients received intravenous hydration. The overall stone treatment success rate was 66.4%. Those with intravenous hydration during the shock wave lithotripsy had significantly smaller stone size, lower serum creatinine levels, lower rate of alpha-blockers use, and higher rate of nonsteroidal anti-inflammatory drug use. Upon multivariate analysis, stone treatment success status postprocedure was significantly associated with stone size (odds ratio 4.118, 95% confidence interval 1.920-8.832, P < 0.0001) and intravenous hydration during the procedure (odds ratio 2.475, 95% confidence interval 1.176-5.208, P = 0.017). Besides small ureteral stone size, concomitant intravenous hydration with 500 mL of normal saline during extracorporeal shock wave lithotripsy was significantly associated with subsequent stone passage. Administering 0.9% NaCl may be a simple and effective measure to improve the treatment efficacy of extracorporeal shock wave lithotripsy.

TIMP2 mediates endoplasmic reticulum stress contributing to sepsis-induced acute kidney injury.

Tissue inhibitor of metalloproteinase 2 (TIMP2) has been recognized as an important biomarker for predicting acute kidney injury (AKI) because of its involvement in the process of inflammation and apoptosis in septic AKI. Endoplasmic reticulum (ER) stress, a condition of disrupted ER homeostasis, is implicated in multiple pathophysiological processes, including kidney disease. Herein, we investigated the correlation between ER stress and septic AKI and further explored how TIMP2 regulated ER stress-mediated apoptosis. To assess the role of TIMP2 in sepsis-induced AKI, we used a cecal ligation and puncture (CLP) model in mice with tubule-specific deficiency of TIMP2 (Ksp-Cre/TIMP2flox/flox ) and their wild-type counterparts. Compared to the wild-type mice, TIMP2-deficient mice demonstrated lower serum creatinine levels and decreased ER stress-mediated apoptosis when subjected to CLP. Interestingly, in human kidney (HK-2) cells, overexpression of TIMP2 caused ER stress, whereas TIMP2knockdown attenuated lipopolysaccharide-induced ER stress and apoptosis. TIMP2 interacted with the binding immunoglobulin protein, an ER chaperone, and facilitates its extracellular secretion, thereby triggering ER stress. This study identified that the deletion of TIMP2 in mouse tubules mitigated sepsis-induced AKI by inhibiting ER stress-mediated apoptosis, which might be a potential therapeutic strategy to alleviate renal injury.

The Prescription Characteristics, Efficacy and Safety of Spironolactone in Real-World Patients With Acute Heart Failure Syndrome: A Prospective Nationwide Cohort Study.

BackgroundRandomized clinical trials of spironolactone showed significant mortality reduction in patients with heart failure with reduced ejection fraction. However, its role in acute heart failure syndrome (AHFS) is largely unknown.AimTo investigate the prescription characteristics, efficacy and safety of spironolactone in real-world patients with AHFS.Methods5,136 AHFS patients who survived to hospital discharge using a nationwide prospective registry in Korea were analyzed. The primary efficacy outcome was 3-year all-cause mortality.ResultsSpironolactone was prescribed in 2,402 (46.8%) at discharge: <25 mg in 890 patients (37.1%), ≥25 mg, and <50 mg in 1,154 patients (48.0%), and ≥50 mg in 358 patients (14.9%). Patients treated with spironolactone had a lower proportion of chronic renal failure and renal replacement therapy during hospitalization and had lower serum creatinine level than those who did not. In overall patients, 3-year mortality was not different in both groups (35.9 vs. 34.5%, P = 0.279). The incidence of renal injury and hyperkalemia was 2.2% and 4.3%, respectively, at the first follow-up visit. The treatment effect of spironolactone on mortality was different across subpopulations according to LVEF. The use of spironolactone was associated with a significant reduction in 3-year morality in patients with LVEF ≤ 26% (33.8 vs. 44.3%, P < 0.001; adjusted HR 0.79, 95% CI 0.64–0.97, P = 0.023), but not in patients with LVEF > 26%.ConclusionsAlthough spironolactone was frequently used at lower doses in real-world practice, use of spironolactone significantly reduced 3-year mortality in patients with severely reduced LVEF with acceptable safety profile. However, our findings remain prone to various biases and further prospective randomized controlled studies are needed to confirm these findings.

Sleep pattern in a group of patients undergoing hemodialysis compared to control

BackgroundPatients with chronic kidney disease progress regularly every year to end-stage renal disease and have to undergo dialysis. Sleep disturbances have been reported to be frequent among patients receiving dialysis and contributing to the increase of their mortality and morbidity. The present research aimed to study the sleep pattern in hemodialysis patients and the risk factors associated. This cross-sectional case-control study included 40 subjects divided into 2 groups: 20 cases recruited from Ain Shams University Hospital’s dialysis unit and 20 in the control group with normal Pittsburgh Sleep Quality Index score matched for age and sex. Both groups were subjected to overnight polysomnography, and the cases group was assessed by the Pittsburgh Sleep Quality Index to determine their sleep quality.ResultsNearly all polysomnographic parameters were significantly abnormal in the cases group except for sleep onset latency (P > 0.05), showing obstructive sleep apnea and periodic limb movement (P value 0.001). Based on their Pittsburgh Sleep Quality Index score, 30% were classified as good sleepers and 70% as bad sleepers. On comparing both groups, a significant difference was found. Poor sleepers had more worse sleep efficiency (62.9%), spent longer time during their sleep in stage 1 (26.6%) with shorter REM onset latency (113.5 ± 99.5), and had a longer duration of illness with lower serum creatinine level compared to good sleepers.ConclusionsThe prevalence of obstructive sleep apnea and periodic limb movement in hemodialysis patients is high; patients with longer time on dialysis are at more risk of sleep disorders, whereas hemoglobin levels, BUN, and other demographic factors do not seem to play a role in sleep disorder. Hence, patients on hemodialysis need to be screened for sleep disorders so as to improve their mortality and morbidity.

Association of serum creatinine levels and risk of type 2 diabetes mellitus in Korea: a case control study

BackgroundReduced skeletal muscle has been suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in skeletal muscle. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea.MethodsWe analyzed a total of 264,832 nondiabetic adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2015 in the Korean National Health Insurance Service Cohort. Hazard ratios for T2DM were calculated.ResultsIn men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association. This association was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose.ConclusionsReduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, although this result was not statistically significant.

Predictors of Renal Recovery among Patients of Obstructive Urolithiasis with Renal FailureA Prospective Observational Study

Introduction: Timely intervention in patients of obstructive uropathy secondary to renal and /or ureteric stones can reduce the morbidity and mortality in such patients. Aim: To determine the factors predicting recovery in patients of urinary stones and obstructive uropathy. Materials and Methods: This prospective observational study was conducted at Shri Mahant Inderesh Hospital, Dehradun, Uttrakhand, India, between December 2018 and June 2020. All patients with renal failure (serum creatinine &gt;1.5 mg/dL) secondary to urinary stones presenting to the Emergency Department were included in the study. Baseline demographic data, clinical, haematological, biochemical and microbiological parameters were recorded at presentation and after Double J Stent (DJS) insertion at postintervention day 1, 3 and 7. Total 40 patients were divided into two groups i.e, recovered (n=25) and non recovered (n=15) groups. Receiver Operating Characteristic (ROC) curves was used to obtain optimal threshold duration of illness, the values of serum creatinine, serum urea, haemoglobin and serum potassium, and time to nadir creatinine for predicting renal recovery. The graphs were made using both Microsoft excel and SPSS software. Results: Out of total 40 pateints, 29 were males and 11 were females. The mean duration of symptoms in the recovered and non recovered groups was 4.64 and 15.53 days, respectively (p-value=0.001). Thirteen out of 15 patients (86.6%) in the non recovered group and 10 out of 25 (40%) in the recovered group had pre-existing co-morbidities (p-value=0.004). Postobstructive diuresis was present in 84% patients in the recovered and 46.6% in the non recovered group (p-value=0.016). The nadir serum creatinine level was 1.26 mg/dL in recovered as compared to 6.08 mg/dL in the non recovered patients (p-value=0.001). The ROC curves were plotted for various parameters in order to find the prognostic accuracy in predicting recovery. The best criteria were symptom duration ≤6 days, serum creatinine at presentation ≤6.2 mg/dL, serum potassium ≤5.5 mg/dL, and haemoglobin level &gt;9.4 gm/dL. Conclusion: Short duration of symptoms (≤6 days), lower serum creatinine levels (≤6.2 mg/dL), lower serum potassium levels (≤5.5 mg/dL), and higher haemoglobin level (&gt;9.4 gm/dL) were found to predict a greater chance of recovery. These factors can help in formulating treatment protocols for early intervention leading to a better prognosis in this subgroup of patients.

Current status of hyperkalemia in dialysis patients in China

Objective: To investigate the prevalence and associated factors of hyperkalemia in dialysis patients. Methods: Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia. Results: A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD (OR=2.25, 95%CI: 1.54-3.30), diabetes mellitus (DM) (OR=1.65, 95%CI: 1.17-2.32), high body mass index (BMI) (OR=1.06, 95%CI: 1.03-1.09), high levels of serum albumin (OR=1.04, 95%CI: 1.01-1.07) and phosphorus (OR=3.12, 95%CI: 2.44-4.00), low levels of serum bicarbonate (OR=0.89, 95%CI: 0.87-0.92), triglycerides (OR=0.76, 95%CI: 0.68-0.85) and creatinine (OR=0.95, 95%CI: 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR=1.38, 95%CI: 1.11-1.72) and beta-blocker (OR=1.32, 95%CI: 1.07-1.64) were associated with hyperkalemia. Conclusions: Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

Effects of Switching from Fenofibrate to Pemafibrate for Asymptomatic Primary Biliary Cholangitis.

The addition of a fibrate to ursodeoxycholic acid (UDCA) is the standard treatment for asymptomatic primary biliary cholangitis (aPBC) with an incomplete response to UDCA. Among the fibrates, bezafibrate and fenofibrate increase the serum creatinine level and reduce the estimated glomerular filtration rate (eGFR). Pemafibrate is an selective peroxisome proliferator-activated receptor alpha modulator (SPPARM-α) mainly metabolized by the liver that was recently approved to treat dyslipidemia. This study confirmed the changes in the biochemical markers after switching from fenofibrate to pemafibrate in aPBC patients. This study examined the effects of switching treatment from fenofibrate to pemafibrate in 16 aPBC patients. The biological parameters of these patients were examined at the initiation of fenofibrate and after switching to pemafibrate, then at 24 and 48 weeks later, respectively. Among patients with aPBC treated with UDCA and fenofibrate, the ALP, GGT, and serum IgM levels decreased significantly (p<0.0001) over 48 weeks. On the other hand, serum creatinine levels increased significantly, and eGFR decreased significantly (p<0.0001). After switching to pemafibrate plus UDCA, patients with aPBC exhibited significantly lower serum creatinine levels (p=0.007) and significantly higher eGFR levels (p=0.014). Pemafibrate has therapeutic efficacy for aPBC patients with an inadequate response to UDCA. Pemafibrate might be another option for aPBC patients given its beneficial effects on renal function, but larger, multicenter studies with a longer follow-up are needed.