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Introduction Chronic kidney disease is a common, progressive illness that is becoming a global public health problem. In patients with kidney dysfunction, the renal excretion of parent drug and/or its metabolites will be impaired, leading to their excessive accumulation in the body. In addition, the plasma protein binding of drugs may be significantly reduced, which in turn could influence the pharmacokinetic processes of distribution and elimination. The activity of several drug-metabolizing enzymes and drug transporters has been shown to be impaired in chronic renal failure. In patients with end-stage renal disease, dialysis techniques such as hemodialysis and continuous ambulatory peritoneal dialysis may remove drugs from the body, necessitating dosage adjustment. Methods Inappropriate dosing in patients with renal dysfunction can cause toxicity or ineffective therapy. Therefore, the normal dosage regimen of a drug may have to be adjusted in a patient with renal dysfunction. Dosage adjustment is based on the remaining kidney function, most often estimated on the basis of the patient's glomerular filtration rate (GFR) estimated by the Cockroft-Gault formula. Net renal excretion of drug is a combination of three processes: glomerular filtration, tubular secretion and tubular reabsorption. Therefore, dosage adjustment based on GFR may not always be appropriate and a re-evaluation of markers of renal function may be required. Discussion According to EMEA and FDA guidelines, a pharmacokinetic study should be carried out during the development phase of a new drug that is likely to be used in patients with renal dysfunction and whose pharmacokinetics are likely to be significantly altered in these patients. This study should be carried out in carefully selected subjects with varying degrees of renal dysfunction. In addition to this two-stage pharmacokinetic approach, a population PK/PD study in patients participating in phase II/phase III clinical trials can also be used to assess the impact of renal dysfunction on the drug's pharmacokinetics and pharmacodynamics. Conclusion In conclusion, renal dysfunction affects more that just the renal handling of drugs and/or active drug metabolites. Even when the dosage adjustment recommended for patients with renal dysfunction are carefully followed, adverse drug reactions remain common.

We aim to detect the effects of sivelestat on renal ischemia-reperfusion associated with AKI and also explore the underlying mechanism. Mice, aged between 8 and 12 weeks, were randomly allocated among four distinct groups, respectively normal saline sham group(C), normal saline surgery group(I), sivelestat (50 mg/kg) sham group(S), sivelestat (50 mg/kg) surgery group(SI) (n=6, each group). In the surgical groups, the renal pedicles of mice were clamped with non-traumatic micro-aneurysm clamps, resulting in ischemia of the kidneys for 45 minutes. This was followed by a period of reperfusion lasting 24 hours. Sham group mice underwent the identical surgery produced without clamping renal pedicles. Mice blood was obtained from eyeballs, and Serum creatinine and blood urea nitrogen levels were measured. After a 24-hour period of reperfusion, the mice were euthanized, and their kidneys were gathered for various analyses, including Western Blot (WB) analysis, RT-PCR, immunofluorescence (IF), hematoxylin and eosin (H&E) staining, and Tunel assay. Pretreatments with sivelestat decreased renal Neutrophil elastase (NE), serum creatinine, and blood urea nitrogen levels after renal ischemia-reperfusion. Sivelestat also reduced histological damage and cell apoptosis in kidneys following ischemia-reperfusion injury (IRI). In addition, the sivelestat administration diminished the levels of mRNA expression of interleukin 6 (IL-6), Macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α in the kidneys during IRI. The kidney tissues of the SI group had significantly mitigated TLR4, Myd88, and NF-κB p-p65 protein expression levels compared to the I group (all P<0.05). We demonstrated a previously unidentified mechanism that sivelestat effectively attenuates AKI-induced renal dysfunction, possibly through suppressing the TLR4/Myd88/ NF-κB pathway.

Background： Chronic kidney disease （CKD） with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods： The present study was a prospective, randomized, double-blind, placebo-controlled, naulticentcr clinical trial. Frorn May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate （eGFR） between 20 and 45 ml ＂rain ~＂ 1.73 m 2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1：1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine （Scr） and eGFR after completion of treatment. The primary endpoints were analyzed using Student＇s t-test or Wilcoxon＇s rank-sum test. The present study reported results based on an intention-to-treat （ITT） analysis. Results： A total of 292 participants underwent the ITT analysis. At 24 weeks, the median （interquartile range） change in Scr was 1.1 （-13.0-24.1） and 11.7 （-2.6-42.9） p, mol/L for the test and control groups, respectively （Z = 2.642, P = 0.008）, and the median change in eGFR was -0.2 （-4.3-2.7） and -2.2 （-5.7-0.8） ml.min-1·1.73 m-2, respectively （Z = -2.408, P = 0.016）. There were no significant differences in adverse events between the groups. Conclusions： Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

Renal dysfunction represents a dreadful complication of advanced liver cirrhosis. In addition to the traditional types of acute kidney injury (AKI) that can occur in the general population, cirrhotics might experience a different kind of renal dysfunction, called hepatorenal syndrome (HRS). The exact definition of HRS is a functional renal dysfunction caused by overactivity of the endogenous vasoactive systems (in particular intrarenal circulation) which lead to reduced renal perfusion. Type I HRS (HRS-1) is characterized by an abrupt deterioration in renal function (in less than 2 weeks), defined by a doubling of baseline sCr to >2.5 mg/dL or a 50% reduction in the initial 24 hrs creatinine clearance to <20 mL/min. Frequent precipitating events leading to HRS-1 are bacterial infections, gastrointestinal hemorrhage, or large-volume paracentesis without adequate albumin administration as well as massive diuretic use. In 2015, the international club of ascites (ICA) revised the definitions and recommendations concerning HRS. The revised definition allows to adopt effective pharmacological therapy based on albumin and vasoconstrictors in an earlier stage thus not influenced anymore by a rigid sCr cut-off value as by the previous definition of HRS-1. The aim of this article was to provide an updated overview of the latest advancements in the field of hepatorenal syndrome and of the recent amendments of the previous definitions of kidney injury in cirrhotic patients.

The aim of the present study was to evaluate the renal outcomes, including the time course of renal function, after elective PCI in patients with advanced renal dysfunction and to assess the predictors of renal dysfunction progression. This is a subanalysis of a previous observational multicenter study that investigated long-term clinical outcomes in patients with advanced renal dysfunction (eGFR < 30 mL/min/1.73 m 2 ), focusing on 151 patients who underwent elective PCI and their long-term renal outcomes. Renal dysfunction progression was defined as a 20% relative decrease in eGFR at 1 year from baseline or the initiation of permanent dialysis within 1 year. Progression of renal dysfunction at 1 year occurred in 42 patients (34.1%). Among patients with renal dysfunction progression, the decrease of renal function from baseline was not observed at 1 month but after 6 months of the index PCI. Baseline eGFR and serum albumin level were significant predictors of renal dysfunction progression at 1 year. Among 111 patients who had not been initiated on dialysis within 1 year, those with renal dysfunction progression had a significantly higher incidence of dialysis initiation more than 1 year after the index PCI than those with preserved renal function ( p < 0.001). Among patients with advanced renal dysfunction who underwent elective PCI, 34.1% showed renal dysfunction progression at 1 year. The decrease in renal function was not observed at 1 month but after 6 months of the index PCI in patients with renal dysfunction progression. Furthermore, patients with renal dysfunction progression had poorer long-term renal outcomes.

To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function - preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, =0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, =0.004; 6.3% vs 13.4%, =0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI.

Background： Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. Methods： This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography （ECG）. Autonomic function was measured based on the heart rate variability （HRV） using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate （eGFR）, and stroke severity was rated according to the National Institutes of Health Stroke Scale （NIHSS）. The Barthel index and modifed Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. Results： In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval （SDANN） index （P = 0.022L very low frequency （VLF） （P = 0.043）, low frequency （LF） （P= 0.023）, and ratio of low-to-high frequency power （LF/HF） （P = 0.001 ） were significantly lower than those in the patients with a normal eGFR. A lnultinomial linear regression indicated that eGFR （t - 2.47, P - 0.014）, gender （t - -3.60, P 〈0.001）, and a history of hypertension （t = -2.65, P = 0.008） were the risk factors of LF/HF; the NIHSS score （SDANN index： t = -3.83, P 〈 0.001 ; VLF： t = -3.07, P = 0.002： LF： t = -2.79, P = 0.006） and a history of diabetes （SDANN index： t = -3.58, P 〈 0.001; VLF： t = -2.54, P = 0.012; LF： t = -2.87, P = 0.004） were independent factors Ibr the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project （t = -2.38, P = 0.018） was related to the SDANN index. Conclusions： Autonomic dysfunction is aggravated with the progression ofeGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfnnction.

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with <5.0 for cardiovascular disease [HR 1.92 (1.08–3.40) for men, 1.71 (1.07–2.71) for women], pneumonia or influenza [2.10 (1.10–4.00) for men, 2.22 (1.17–4.19) for women], and digestive diseases [for men; 3.81 (1.49–9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary β2-MG of ≥1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

Objective: To assess renal function in combat patients at the time of arrival from Balochistan in Accident & Emergency (A&E) of an ‘A’ Class Military Hospital. Study Design: Retrospective observational study with analysis to find correlation between measurable variables and glomerular filtration rate. Place and Duration Of Study: Combined Military Hospital Malir Cantonment, Karachi, from October 2015 to October 2018. Material and Methods: All patients with major injuries (New Injury Severity Score NISS ≥16) were included in the study to assess kidney function by calculating their estimated glomerular filtration rate (eGFR) using serum creatinine. Correlation was calculated between eGFR and other variables which were pulse, mean arterial pressure, temperature and haemoglobin. Results: 75 patients were brought to A&E. 14 (18.66%) were brought in dead. There were 44 (58.6%) gunshot wounds, 14 (18.6%) blast injuries and 17 (22.6%) accidents post ambush attack. 26 (34.66%) were included in the study, with NISS ≥16. All patients were male with mean age 29.73 ± 5.08. 20 (77%) patients were fluid resuscitated in pre-hospital setting whereas 6 (23%) were not. Statistically significant correlations were found among eGFR and pulse rate, body temperature, mean arterial pressure, hemoglobin and NISS. 6 out of 26 patients not resuscitated in pre-hospital setting had a median eGFR of 53.5, as compared to median eGFR of 70 in 20 patients who were resuscitated before evacuation to CMH Malir, in the field medical units. Conclusion: Fluid resuscitation in the field lowers the possibility of renal dysfunction.

Abstract This study was conducted to evaluate the protective role of extracted natural antioxidants from black rice and their effect on kidney failure and renal cirrhosis caused by ethanol-induced toxicity. Antioxidant activity in terms of total phenol content, flavonoid compounds and anthocyanin, as well as antioxidant capacity, was determined in an extract of black rice. The findings noted that the black rice extract contained high amounts of antioxidant activity and capacity. Total phenolic compounds from black rice extract were fractionated using HPLC and the results showed that ferulic, sinapic, ascorbic, salicylic and coumaric acids were the highest in the extract. Biological experiments were performed on male albino adult rats (40 animals, 10 rats for each group), divided into four groups. After five weeks, kidney functions and protein fractions were assessed. In addition, superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) enzyme activities were determined in all groups. The results found that kidney function, total protein, albumin and globulin were affected by renal dysfunction and renal fibrosis in the positive control (PC), whereas groups 3 and 4 noted an improvement in renal function nearly or equal to the healthy rats which were fed on a basal diet. Furthermore, the PC group showed significantly decreased levels of enzymatic antioxidants, namely SOD and GSH with a concomitant elevated MDA level compared with those in the negative rats fed on a basal diet. Groups 3 and 4 also reported improvements in enzyme activity. These results were further supported by histopathological findings which revealed a curative effect in groups 3 and 4, which avoided renal dysfunction and renal fibrosis from ethanol-induced toxicity. From the results, it can be said that the black rice extract with the highest amounts of antioxidants led to improvements in all parameters, especially kidney function, total protein, albumin, and globulin, in addition to enzyme activity. Therefore, black rice can be recommended as a benefit to general health. Resumo Este estudo foi conduzido para avaliar o papel protetor dos antioxidantes naturais extraídos do arroz-preto e seu efeito na insuficiência renal e cirrose renal causada pela toxicidade induzida pelo etanol. A atividade antioxidante em termos de teor de fenóis totais, compostos flavonoides e antocianinas, bem como a capacidade antioxidante, foi determinada em um extrato de arroz-preto. As descobertas observaram que o extrato de arroz-preto continha grandes quantidades de atividade e capacidade antioxidante. Os compostos fenólicos totais do extrato de arroz-preto foram fracionados por HPLC e os resultados mostraram que os ácidos ferúlico, sinápico, ascórbico, salicílico e cumárico foram os mais elevados no extrato. Experimentos biológicos foram realizados em ratos adultos albinos machos (40 animais, 10 ratos para cada grupo), divididos em quatro grupos. Após cinco semanas, as funções renais e frações proteicas foram avaliadas. Além disso, as atividades das enzimas superóxido dismutase (SOD), glutationa (GSH) e malondialdeído (MDA) foram determinadas em todos os grupos. Os resultados mostraram que a função renal, proteína total, albumina e globulina foram afetadas por disfunção renal e fibrose renal no controle positivo (CP), enquanto os grupos 3 e 4 observaram uma melhora na função renal quase ou igual aos ratos saudáveis que foram alimentados em uma dieta básica. Além disso, o grupo PC apresentou níveis significativamente diminuídos de antioxidantes enzimáticos, ou seja, SOD e GSH com um nível concomitante de MDA elevado em comparação com aqueles nos ratos negativos alimentados com uma dieta basal. Os grupos 3 e 4 também relataram melhorias na atividade enzimática. Esses resultados foram ainda apoiados por achados histopatológicos que revelaram um efeito curativo nos grupos 3 e 4, que evitou a disfunção renal e fibrose renal por toxicidade induzida pelo etanol. A partir dos resultados, pode-se dizer que o extrato de arroz-preto com maior quantidade de antioxidantes levou a melhorias em todos os parâmetros, principalmente função renal, proteína total, albumina e globulina, além da atividade enzimática. Portanto, o arroz-preto pode ser recomendado como um benefício para a saúde geral.