Impact on grafted kidney function of rocuronium-sugammadex vs cisatracurium-neostigmine strategy for neuromuscular block management. An Italian single-center, 2014-2017 retrospective cohort case-control study

Background The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation. Methods A single-center, 2014-2017 retrospective cohort case-control study was performed. A total of 350 patients undergoing kidney transplantation, equally divided between a sugammadex group (175 patients) and a neostigmine group (175 patients), were considered. Postoperative kidney function, evaluated by monitoring of serum creatinine and urea and estimated glomerular filtration rate (eGFR), was the endpoint. Other endpoints were anesthetic and surgical times, post-anesthesia care unit length of stay, postoperative intensive care unit admission, and recurrent NMB or complications. Results No significant differences in patient or, with the exception of drugs involved in NMB management, anesthetic, and surgical characteristics, were observed between the two groups. Serum creatinine (median [interquartile range]: 596.0 [478.0-749.0] vs 639.0 [527.7-870.0] μmol/L, p = 0.0128) and serum urea (14.9 [10.8-21.6] vs 17.1 [13.1-22.0] mmol/L, p = 0.0486) were lower, while eGFR (8.0 [6.0-11.0] vs 8.0 [6.0-10.0], p = 0.0473) was higher in the sugammadex group than in the neostigmine group after surgery. The sugammadex group showed significantly lower incidence of postoperative severe hypoxemia (0.6% vs 6.3%, p = 0.006), shorter PACU stay (70 [60-90] min vs 90 [60-105] min, p < 0.001), and reduced ICU admissions (0.6% vs 8.0%, p = 0.001). Conclusions Compared to cisatracurium-neostigmine, the rocuronium-sugammadex strategy for reversal of NMB showed a better recovery profile in patients undergoing kidney transplantation.

Gouty arthritis and kidney function outcomes and serum uric acid level variations in obese patients following bariatric surgery

Background Obesity is an independent risk factor for chronic kidney disease (CKD) and is the strongest known modifiable risk factor for hyperuricemia and gout. We aimed to discover the outcome of serum uric acid (SUA), gouty arthritis, and kidney function in obese patients after bariatric surgery and possible links with BMI variations. Methods Retrospective study has been performed in National Hospital in Riyadh, KSA, between Jan. 2018 to Jan. 2020. We studied only 98 patients who met our inclusion criteria. Patients followed-up at 1 month (for gouty attack only) postoperative, 3 months postoperative, and 6 months postoperative for body mass index (BMI), serum creatinine, dipstick urinalysis, SUA, and estimated glomerular filtration rate (eGFR). Radiological studies, medical history, follow up radiological studies, and clinical follow up were obtained from the hospital data system. Results A total of 98 patients with mean eGFR were 90.65 ± 29.34 ml/min/1.73 m2, mean SUA 5.56 ± 1.84 mg/dl, and mean BMI was 45.28 ± 7.25 kg/m2, at surgery. Mean BMI had decreased significantly to 38.52 ± 6.05 kg/m2 at 3 months and to 34.61 ± 5.35 kg/m2 at 6 months (P < 0.001). The mean GFR had improved significantly (99.14 ± 23.32 ml/min/1.73 m2) at 6 months (P < 0.001). Interestingly, proteinuria had resolved in 17 patients out of 23 patients at 6 months. Number of gouty attacks was decreased during the first month post-surgery (P < 0.001). SUA level was significantly decreased (4.32 ± 1.27 mg/dl) (P < 0.001). SUA showed significant negative correlations with eGFR at 3 months and positively significant correlations with BMI at 3 and 6 months. By multinomial logistic regression, BMI and initial eGFR were the independent predictive variables for the outcome of eGFR at 6 months, while male gender and initial SUA were the independent predictive variables on the outcome of SUA at 6 months. Postoperatively in gouty arthritis patients, the number of joints affected, patient global VAS assessment, and number of gouty attacks were significantly reduced (P < 0.001). Conclusion Bariatric surgery has been associated with reduction of BMI and subsequently reduction of SUA levels, gouty attacks, and improvement of eGFR.

Glomerular function and urinary biomarker changes between vancomycin and vancomycin plus piperacillin-tazobactam in a translational rat model.

Clinical studies have reported additive nephrotoxicity associated with the combination of vancomycin (VAN) and piperacillin-tazobactam (TZP). This study assessed differences in glomerular filtration rate (GFR) and urinary biomarkers between rats receiving VAN and those receiving VAN+TZP. Male Sprague-Dawley rats (n=26) were randomized to receive 96 hours of intravenous VAN at 150mg/kg/day, intraperitoneal TZP at 1400 mg/kg/day, or VAN+TZP. Kidney function was evaluated using fluorescein-isothiocyanate sinistrin and a transdermal sensor to estimate real-time glomerular filtration rate (GFR). Kidney injury was evaluated via urinary biomarkers including kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to a saline control, only rats in the VAN group showed significant declines in GFR by day 4 (-0.39 mL/min/100 g body weight, 95% CI: -0.68 to -0.10, p=0.008). When the VAN+TZP and VAN alone treatment groups were compared, significantly higher urinary KIM-1 was observed in the VAN alone group on day 1 (18.4 ng, 95% CI: 1.4 to 35.3, p=0.03), day 2 (27.4 ng, 95% CI: 10.4 to 44.3, p=0.002), day 3 (18.8 ng, 95% CI: 1.9 to 35.8, p=0.03), and day 4 (23.2 ng, 95% CI: 6.3 to 40.2, p=0.007). KIM-1 was the urinary biomarker that most correlated with decreasing GFR on day 3 (Spearman’s rho: -0.45, p = 0.022) and day 4 (Spearman’s rho: -0.41, p = 0.036). Kidney function decline and increased KIM-1 were observed among rats that received VAN only, but not TZP or VAN+TZP. Addition of TZP to VAN does not worsen kidney function or injury in our translational rat model.

Association Between Baseline Buccal Telomere Length and Progression of Kidney Function: The Health and Retirement Study

We aimed to evaluate associations of baseline telomere length with overall and annual change in estimated glomerular filtration rate (eGFR) and trajectory of kidney function during an 8-year follow-up. A total of 3,964 participants of the Health and Retirement Study (HRS) were included. We identified three trajectory groups of kidney function: consistently normal (n=1,163 or 29.3%), normal to impaired (n=2,306 or 58.2%), and consistently impaired groups (n=495 or 12.5%). After controlling for age, sex, race, education, smoking, drinking, diabetes, heart disease, blood pressure, body mass index, total cholesterol, and hemoglobin A1c, participants with longer telomere length were 20% less likely (odds ratio [OR]=0.80, 95% confidence interval [CI]: 0.69-0.93, P=0.003) to have a normal to impaired kidney function trajectory than a consistently normal function trajectory. Telomere length was not associated with changing rate of eGFR over 8 years (P=0.45). Participants with longer telomere length were more likely to have consistently normal kidney function.

Npt2a as a target for treating hyperphosphatemia

Hyperphosphatemia results from an imbalance in phosphate (Pi) homeostasis. In patients with and without reduced kidney function, hyperphosphatemia is associated with cardiovascular complications. The current mainstays in the management of hyperphosphatemia are oral Pi binder and dietary Pi restriction. Although these options are employed in patients with chronic kidney disease (CKD), they seem inadequate to correct elevated plasma Pi levels. In addition, a paradoxical increase in expression of intestinal Pi transporter and uptake may occur. Recently, studies in rodents targeting the renal Na+/Pi cotransporter 2a (Npt2a), responsible for ∼70% of Pi reabsorption, have been proposed as a potential treatment option. Two compounds (PF-06869206 and BAY-767) have been developed which are selective for Npt2a. These Npt2a inhibitors significantly increased urinary Pi excretion consequently lowering plasma Pi and PTH levels. Additionally, increases in urinary excretions of Na+, Cl− and Ca2+ have been observed. Some of these results are also seen in models of reduced kidney function. Responses of FGF23, a phosphaturic hormone that has been linked to the development of left ventricular hypertrophy in CKD, are ambiguous. In this review, we discuss the recent advances on the role of Npt2a inhibition on Pi homeostasis as well as other pleiotropic effects observed with Npt2a inhibition.

The Effect of Diabetes and the Diabetogenic TBC1D4 p.Arg684Ter Variant on Kidney Function in Inuit in Greenland

ObjectiveDiabetes prevalence in Greenland is high and increasing. The aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting.Research Design and MethodsHealth survey data and TBC1D4 genotypes from 5,336 Greenlanders was used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR<60 ml/min/1.73m2), comparing individuals with and without diabetes. Using baseline and follow-up data from individuals who participated in two surveys we examined the effect of diabetes on eGFR and urinary albumin creatinine ratio (UACR) at follow-up, stepwise adjusting for baseline confounders including the TBC1D4 variant.ResultsA total of 9.3% had diabetes of the 3,909 participants with complete data. Albuminuria and CKD was found in 27.6% and 9.5% among those with and without diabetes respectively. Diabetes was associated with increased risk of albuminuria (OR(95% CI) = 2.37 (1.69,3.33) p<0.001) and the TBC1D4 variant protected against albuminuria (OR(95% CI) = 0.44 (0.22,0.90) p=0.02) in a multivariable model. Neither diabetes nor the TBC1D4 variant significantly associated with CKD. Diabetes was not associated with changes in eGFR or UACR over a median of 11.3 years.ConclusionDiabetes conferred increased risk of albuminuria and the TBC1D4 variant was associated with decreased risk of albuminuria, but neither were associated with CKD. The presence/absence of diabetes did not predict changes in eGFR and UACR in longitudinal analyses. The potential renoprotective association of the TBC1D4 variant on albuminuria calls for further studies.