Plasma Creatinine Concentration Research Articles

#1973 Factors conditioning cisplatin nephrotoxicity

Abstract Background and Aims Cisplatin is an antitumor drug whose use is significantly limited by its nephrotoxicity. Knowledge of the factors that determine or condition the pathogenesis of cisplatin-induced AKI will help to prevent or reduce nephrotoxic outcomes and improve safety during cisplatin treatment. Specifically, we aimed to study the impact of different factors (dehydration, hypertension, age and combinations of the former) on a pre-clinical model of AKI induced by a low dose of cisplatin. Method Young Wistar rats, young spontaneously hypertensive rats (SHR), and aged Wistar rats were divided into two experimental groups: Blood and 24-hour urine samples were collected, and renal function (plasma creatinine, plasma urea and urine protein levels) and dehydration parameters (weight loss, skin elasticity, haematocrit, plasma osmolality, urine flow and urine concentration) were monitored for each animal at three different timepoints: basal time (B), at the end of the dehydration period (D0), and 4 days after cisplatin administration (D4, day of maximum kidney damage). Results After 48 h water deprivation, dehydration was evinced by loss of weight, reduced skin elasticity, increases in plasma osmolality and haematocrit, urine flow reduction and highly concentrated urine (with elevated density and osmolality). A single, low dose of cisplatin induced minimal loss of renal function in young normohydrated Wistar rats that was not worsened by previous acute dehydration resulting from 48 h water deprivation. Interestingly, although renal function was fully preserved when cisplatin was administered to hypertensive rats under normohydrated conditions, a cisplatin-induced AKI (with significant increases in plasma creatinine, plasma urea and proteinuria) was developed in hypertensive rats when animals were previously forced to dehydration. Aged Wistar rats with free access to drinking water showed an important loss of renal function after cisplatin administration (as supported by increases in plasma creatinine and urea concentration). This effect was significantly amplified when aged animals were dehydrated at the time of cisplatin administration. Conclusion Our results suggest that age is an important factor conditioning cisplatin nephrotoxicity. Hypertension or dehydration in fully competent young rats are not in itself significant risk factors for AKI. However, when dehydration is combined with other comorbidity (age or hypertension) the risk of cisplatin-induced AKI is significantly increased. In perspective, our animal models reproducing conditions of increased vulnerability to cisplatin-induced AKI provide useful tools not only for the identification of predictive biomarkers pre-emptively detecting individuals at high risk, but also to assess preventive strategies potentially useful for vulnerable individuals. This study was supported by Project PI21/01226, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, and a grant from the Consejería de Educación, Junta de Castilla y León (IES160P20), Spain, co-funded by FEDER funds. Noelia Diaz-Morales is recipient of a Juan de la Cierva-Formación postdoctoral contract (FJC2020-043205-I) funded by MCIN/AEI/10.13039/501100011033 and European Union “NextGenerationEU/PRTR”.

#1436 Donor plasma cystatin C, but not creatinine, is associated with measured GFR at one year after kidney transplantation

Abstract Background and Aims Although widely used during deceased kidney donor selection, donor plasma creatinine has limited capacity to predict future recipient kidney graft function. Cystatin C is a muscle-mass independent kidney function marker that could serve as alternative for this purpose. However, the association between donor cystatin C and subsequent recipient graft function remains unclear. We aim to assess the association of pre-donation cystatin C concentrations with recipient iothalamate-measured GFR (mGFR) one year after kidney transplantation and compare it to the association of donor creatinine concentrations. Method All deceased kidney donors, within the affiliated donation region of the University Medical Center Groningen (UMCG), who donated at least one kidney to a kidney transplant recipient (KTR) affiliated to the same hospital during a period of 15 years (2004-2019) were included. We excluded all subjects with missing data on donor plasma cystatin C or recipient mGFR at 1 year. Donor plasma creatinine concentrations were measured using an enzymatic assay, while donor cystatin C concentrations were measured using a validated particle-enhanced turbidimetric immunoassay (Roche). Associations of donor plasma creatinine and cystatin C concentrations with recipients’ mGFR one year after transplant were assessed using linear regression. Results A total of 53 deceased kidney donors (55% male, age 47 ± 18 years, 47% donation after circulatory death) donated a kidney to 53 kidney transplant recipients (55% male, age 57 ± 12 years). Median pre-donation plasma creatinine and cystatin C concentrations were 64 [55 to 82] μmol/L and 0.64 [0.51 to 0.82] mg/L respectively. Mean recipient mGFR one year after transplantation was 52.7 ± 17.1 ml/min. In univariable linear regression, higher donor cystatin C was significantly associated with lower mGFR (β −0.42, 95% CI: −0.67 to −0.16, p = 0.002), while donor creatinine was not associated (β −0.03 95% CI: −0.32 to 0.25, p = 0.81). The association between donor cystatin C and recipients’ mGFR remained independent of adjustment for potential confounders, including donor sex and age, t (p = 0.008). Conclusion Higher donor cystatin C, but not creatinine, is associated with lower measured GFR one year after kidney transplant. Consequently, donor cystatin C could be valuable for inclusion in the pre-transplant evaluation of deceased kidney donors.

#1413 High performance of ACLARA calculator of rat creatinine clearance for the chronic follow up of renal function

Abstract Background and Aims A neural network-based calculator to estimate rat creatinine clearance (ClCr), as a measurement of the glomerular filtration rate (GFR), from paired plasma creatinine concentration and body weight data has been recently developed [1]. Like human GFR estimating formulae, ACLARA averts long experimental procedures and reduces animal stress (by obviating the use of individual isolation in metabolic cages). This tool is publicly available for free use among the scientific community (https://idal.uv.es/aclara/). When collated with experimentally measured ClCr, ACLARA performs very well at comparing experiments in the whole, showing almost identical behavior of all experimental groups and conditions. Yet, ACLARA was trained mostly with data from short experiments involving acute changes in renal function, and from young rats. Fewer data from older animals was included in the development of the calculator. Thus, its field performance on longer evolution of renal function in adult rats has not yet been sufficiently validated. Accordingly, the aim of this work was to deepen in the assessment of ACLARA in the long-term evolution of rat ClCr. Method The evolution of measured (mClCr) versus ACLARA-estimated ClCr (eClCr) was compared at different time points over a period of 3 months in 20 male Wistar rats with chronic renal damage and 8 age-matched controls. In total, 176 data pairs of mClCr and eClCr were obtained. On the one hand, mClCr was determined by the usual experimental procedure [2]. Briefly, rats were allocated in metabolic cages to obtain 24-hour urine samples and urine flow (UF). Creatinine concentration was measured in the urine (Cru) and plasma (Crp) by a colorimetric assay based on the Jaffe's reaction, and mCrCl was then calculated as Cru x UF / Crp. On the other hand, eClCr was estimated with the ACLARA calculator from the corresponding Crp and body weight data. A Pearson's correlation study between mClCr and eClCr was carried out. Results Our results reveal that the information provided by the 90-day evolution of mClCr and eClCr is virtually identical at the whole experiment level (see Fig. 1). Furthermore, ACLARA seems to provide slightly more coherent and homogeneous information, as the considerable experimental error introduced by urine collection is averted in eClCr but present in mClCr. At the individual data level, ACLARA-estimated values are slightly lower than the corresponding measurements. The correlation between mClCr and eClCr was highly significant (r Pearson= 0.83; p < 0.0001). Conclusion ACLARA shows high performance at estimating CrCl in rats of growing age. Our results support its use also in chronic studies in which renal function must be evaluated. Funding This research was funded by grants from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación (PI21/01226 and PI21/00548 co-funded by the European Union; and RICORS2040, RD21/0005/0004, co-funded by the European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)) and from Consejería de Educación, Junta de Castilla y León (IES160P20), co-funded by FEDER funds. Joana Mercado-Hernández is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

Dapagliflozin Stimulates Renal Ammonia Excretion in Rats

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs that induce glycosuria and are used to treat type 2 diabetes mellitus, moreover it has also been used in other conditions such as heart failure and atherosclerosis. However, little is known about the effects of these drugs on renal function. Considering that the maintenance of acid-base balance is closely related to renal physiology, in this study we evaluated the influence of chronic use of dapagliflozin on global renal function and urinary excretion of ammonia and titratable acids. Objective: To evaluate global renal function and urinary acid excretion (ammonia and titratable acid) in male Wistar rats chronically treated with dapagliflozin. Methods: 3-month-old male Wistar rats were randomized to control (C) and dapagliflozin (D) groups. Animals in group D received dapagliflozin (3 mg/kg, gavage) for 4 weeks. All animals were given food and water ad libitum throughout the experimental protocol. At 4 months of age, animals were placed in metabolic cages for 24-hour urine collection followed by blood sampling. Plasma concentrations of creatinine, sodium, potassium, urea, pH, pCO2, and bicarbonate were evaluated. The following were also evaluated: body weight, water intake, urine flow, and excretion of ammonia, titratable acids, glucose, and protein. Protocol approved by CEUA-UNIFESP number: 5985180423. Values expressed as mean ± standard error; number of animals per group: 6. Results: No significant changes were observed in blood gas parameters: pH (C: 7.33±0.043; D: 7.36±0.027), pCO2 (C: 53.30±2.40; D: 52.67±3.63 mmHg) and HCO3− (C: 27.07±1.31; D: 29.75±1.72 mEq/L) and no significant changes in plasma creatinine concentration (C: 0.41±0.04; D: 0.40±0.04mg/dl), Na+ (C: 144±0.47; D: 137±2.04 mmol/l) and K+ (C: 4.30±0.21; D: 4.16±0.20 mmol/l). We observed a significant increase in urine flow (C: 0.027±0.006; D: 0.068±0.005 mL/min/kg), possibly associated with intense glycosuria (C: 0.017±0.005; D: 8.97±0.51 g/24h). The significant increase in plasma urea concentration (C: 39.17±2.57; D: 48.83±1.27 mg/dL) and proteinuria (C: 11.04±0.30; D: 15.79±0.56 mg/24h) may indicate some renal impairment. Considering the marked increase in urinary excretion of ammonia (C: 0.65±0.05; D: 3.49±2.31 mEq/24h) and titratable acids (C: 0.180±0.036; D: 0.628±0.078 mEq/24h), we can conclude that the drug-induced glycosuria may lead to biochemical adaptations to maintain blood glucose levels within the normal range, at the expense of increased metabolic acid production. However, further experiments are needed to confirm this hypothesis. CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dietary crude protein and protein solubility manipulation enhances intestinal nitrogen absorption and mitigates reactive nitrogen emissions through gut microbiota and metabolome reprogramming in sheep

Dietary nutrient manipulation (e.g. protein fractions) could lower the environmental footprints of ruminants, especially reactive nitrogen (N). This study investigated the impacts of dietary soluble protein (SP) levels with decreased crude protein (CP) on intestinal N absorption, hindgut N metabolism, fecal microbiota and metabolites, and their linkage with N metabolism phenotype. Thirty-two male Hu sheep, with an age of six months and an initial BW of 40.37 ± 1.18 kg, were randomly assigned to four dietary groups. The control diet (CON), aligning with NRC standards, maintained a CP content of 16.7% on a dry matter basis. Conversely, the experimental diets (LPA, LPB, and LPC) featured a 10% reduction in CP compared with CON, accompanied by SP adjustments to 21.2%, 25.9%, and 29.4% of CP, respectively. Our results showed that low-protein diets led to significant reductions in the concentrations of plasma creatinine, ammonia, urea N, and fecal total short-chain fatty acids (SCFA) (P < 0.05). Notably, LPB and LPC exhibited increased total SCFA and propionate concentrations compared with LPA (P < 0.05). The enrichment of the Prevotella genus in fecal microbiota associated with energy metabolism and amino acid (AA) biosynthesis pathways was evident with SP levels in low-protein diets of approximately 25% to 30%. Moreover, LPB and LPC diets demonstrated a decrease in fecal NH4+-N and NO2--N contents as well as urease activity, compared with CON (P < 0.05). Concomitantly, reductions in fecal glutamic acid dehydrogenase gene (gdh), nitrite reductase gene (nirS), and nitric oxide reductase gene (norB) abundances were observed (P < 0.05), pointing towards a potential reduction in reactive N production at the source. Of significance, the up-regulation of mRNA abundance of AA and peptide transporters in the small intestine (duodenum, jejunum, and ileum) and the elevated concentration of plasma AA (e.g. arginine, methionine, aspartate, glutamate, etc.) underscored the enhancement of N absorption and N efficiency. In summary, a 10% reduction in CP, coupled with an SP level of approximately 25% to 30%, demonstrated the potential to curtail reactive N emissions through fecal Prevotella enrichment and improve intestinal energy and N utilization efficiency.

The association between opioid dose and kidney function and clinical outcome in critically ill patients, a retrospective cohort study

BackgroundCritically ill patients are prone to develop acute kidney injury. Apart from the nervous system, opioid receptor expression is highest in the kidneys, although their function in the kidney is unclear. In view of the frequent use of opioids, high expression of its receptors in the kidney and high incidence of AKI in critically ill patients, these may be interconnected. AimTo determine the association between opioid dose and kidney function and outcome in critically ill patients. MethodsIn this retrospective cohort study adult patients admitted to ICU (2013–2020), were eligible. The association between opioid administration and kidney function and mortality were determined using total cumulative dose and quartiles. Demographics, disease severity, and sedatives dose were covariates. Results2824 patients (median [IQR] age 64 [53–71] years, ICU-LOS of 8 [4–15] days, 64 % male) were included. Cumulative opioid dose (day 1–3 of ICU-admission), corrected for covariates, was not associated with change in plasma creatinine concentrations: (unstandardized-B for every mg/hour opioids given these days (Confidence Interval): -0.15 (−0.36–0.06) μmol/L, p = 0.15), or urine output: -0.42 (−1.41–0.56) mL for (p = 0.40). Mortality increased from 3.5 % in Quartile 1 of cumulative opioid dose to 10.3 % in Q4. Covariate-corrected mortality hazard ratios compared with Q1 were: Q2: 1.12 (0.85–1.48), p = 0.41, Q3: 1.58 (1.19–2.09), p = 0.001 and Q4: 1.50 (1.06–2.12), p = 0.021. ConclusionsIn critically ill patients, opioid dose was not associated with a change in kidney function. However, opioid dose was associated with an increased ICU-LOS and mortality risk.

A study of size-selective renal elimination using a novel human model

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was −0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Drinking magnetized water alters blood constituents, and structure of spleen and kidney in rabbits

This study aimed to investigate the effect of magnetic field on physicochemical properties of water and evaluating the effects of the magnetized water (MW ) on the productive performance, liver enzymes, spleen and kidney structure of rabbits. Water samples were collected to determine pH and electrical conductivity (EC), and water structure was investigated by Transmission Electron Microscopy (TEM). Twenty-four weaned Rex rabbits, 21 d old, were allotted into two experimental groups: the first group was assigned as control, received regular tap water (TW), and the treated group, received MW, for 5 weeks. Productive traits were recorded weekly and at the end of the experiment, blood samples, spleen and kidney were collected for examinations. Results showed that pH and EC of MW were higher than those of TW. In addition, the arrangement MW cluster showed a unique alteration on the nano-scale. Growth performance indicators were similar in both experimental treatments, except FCR of the MW rabbits was better than that of the TW rabbits. The MW had no significant effect on plasma concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine in growing Rex rabbits received MW in comparison with those received regular TW. Spleen histological structure of rabbits of both groups was normal. However, the epithelial cells lining renal tubules of kidneys of rabbits in MW group appeared large with basophilic nuclei in comparison with TW group. Conclusively, magnetic field alters the physicochemical properties of water. The MW may consequently increase blood glucose level and spleen weight % and enhance kidney structure in growing rabbits. Moreover, more studies are still needed to know the benefits of providing the magnetized water to ‎animals. ‎

SLC6A8 creatine transporter deficiency can be detected by plasma creatine and creatinine concentrations

Creatine transporter deficiency has been described with normal or uninformative levels of creatine and creatinine in plasma, while urine has been the preferred specimen type for biochemical diagnosis. We report a cohort of untreated patients with creatine transporter deficiency and abnormal plasma creatine panel results, characterized mainly by markedly decreased plasma creatinine. We conclude that plasma should be considered a viable specimen type for the biochemical diagnosis of this disorder, and abnormal results should be followed up with further confirmatory testing.

Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. Thirty-six euthyroid client-owned cats with CKD. Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound-diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. Ultrasound-diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log-transformed fibroblast growth factor-23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P < .001) and decreasing body weight (.02 ± .01 kg/month; P < .001) over time. Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats.

The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study.

Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 μmol/L to 19.69 μmol/L, and saliva, from 59.00 μmol/L to 13.70 μmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.

Effect of postpartum drenching on plasma parameters of cows at a large-scale dairy farm.

The aim of the present study was to explore the influence of postpartum drenching with a feed additive on the plasma concentration of biochemical parameters while factoring in prepartum rumination times (RT). One hundred and sixty-one cows were fitted with a Ruminact© HR-Tag approximately 5 days before calving. Drenching and control groups were established based on calving dates. Animals in the drenched group were treated three times (Day 1/day of calving/, Day 2, and Day 3 postpartum) using a feed additive containing calcium propionate, magnesium sulphate, yeast, potassium chloride and sodium chloride mixed in approximately 25 L of lukewarm tap water. Blood samples were collected on Days 1, 2, 3, 7 and 12. Cows with below the average RT were categorised as "low rumination" and those above it as "high rumination" animals. Drenching decreased the plasma concentrations of total protein, urea and creatinine and increased the levels of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and chloride. Low rumination time prepartum resulted in higher concentrations of beta-hydroxybutyrate, total protein and activities of alkaline phosphatase and GGT, while it decreased the activity of ALT and the concentrations of calcium, magnesium, sodium and potassium. The day of lactation had an effect on all parameters except for potassium.

Disentangling the dynamic interplay between muscle damage and energetics in male boxers during a short training block.

Boxing is a combat sport linked to muscle damage (e.g., soreness, rising creatine kinase [CK]) and energetic biomarkers (e.g., urea, glucose). These factors have not, however, been examined dynamically in terms of day-to-day, lagged and reciprocal effects during normal training. This study investigated the dynamic interplay between muscle damage and energetics in male boxers during a short training block. Thirteen amateur boxers were monitored over 16 consecutive days during early-season training. The participants were assessed each morning for plasma CK, urea, glucose, and creatinine (days 1 and 16 only) concentrations, before self-reporting muscle soreness (1-10 scale). Within-person contemporaneous (lag-0) and temporal (lag-1) networks were estimated using multilevel vector autoregression. Muscle soreness, CK, urea, and glucose presented different trajectories with training, but with some heterogeneity reflecting within-person variances (47% to 78%). The contemporaneous network yielded a significant positive edge (or correlation) between CK and soreness (r = 0.44), along with negative CK-glucose and glucose-urea edges. More significant edges emerged in the temporal network, with soreness linked to CK (r = 0.19), glucose (r = -0.28) and urea (r = 0.22), whilst the CK-glucose edge sign switched. In summary, daily fluctuations in muscle damage and energetic activity, which presented in a normal physiological range, were highly variable among boxers during early-season training. Within-person networks indicated some interrelatedness between CK, soreness, urea, and glucose, although the nature and presence of these relationships were contingent on temporal ordering. These inconsistences reflect the pleiotropy of energetic biomarkers in training and recovery.

KIDNEY ULTRASOUND PARAMETERS AND RENAL BLOOD BIOCHEMISTRY MARKERS IN POST-HEMORRHAGIC STROKE HYPERTENSIVE SURVIVORS

Introduction. Hemorrhagic stroke is a serious and devastating complication of arterial hypertension, which leads to increased mortality in survivors even after the early recovery period. Being other target organs for arterial hypertension, kidneys take part in blood pressure regulation. Investigation of their peculiarities in such patients may provide valuable data on possible reasons of poor long-term prognosis in this category of patients.&#x0D; The aim of the study: to compare kidney ultrasound parameters and renal blood biochemistry tests between the post-hemorrhagic stroke hypertensive subjects in a stable phase of recovery period and the patients with arterial hypertension who had no cerebrovascular and cardiovascular events.&#x0D; Materials and methods. There were 100 subjects enrolled into the study. They formed two investigatory groups: the main (n=64; age – 52,2±8,41 years, M±SD years) and the control (n=36; age – 51,8±5,92 years) one. Hypertensive patients of the main group developed hemorrhagic stroke – subarachnoid hemorrhage (SAH) (n=42) or intracerebral hemorrhage (ICH) (n=22) – ≥6 months prior to the examination conducted at this study. The control group consisted of patients with non-complicated arterial hypertension. In both groups of patients, the kidney ultrasound parameters and blood plasma urea, creatinine and uric acid concentration levels were determined. Estimated glomerular filtration rate (eGFR) was calculated.&#x0D; Results. The indices of kidney ultrasound parameters in the main group and the control group were the following ones, respectively: the pole-to-pole size of the right kidney was 9,96±1,05 and 11,63±1,26 cm, the same size of the left kidney – 10,39±0,93 and 11,95±1,23 cm, p&lt;0,01 for both pairs. Among the biochemistry blood plasma indices, uric acid concentration reached significant difference as well – 411,21±60,36 and 360,91±75,3 µmol/L in the relevant groups, respectively (p=0,04). On the other hand, eGFR did not show the difference between the study groups. The main group was characterized by a higher prevalence of kidney stone formation – OR 5,00 (95% CI, 1,83-13,65). The statistically significant higher incidence rate of calculus development was identified in two subgroups of the main group as well: for SAH – OR 3,08 (95% CI, 1,05-9,02), for ICH – OR 13,33 (95% CI, 3,69-48,15). When comparing to the control group, kidney cyst identification rate in the SAH subgroup referred to OR 3,08 (95% CI, 1,05-9,02), while kidney pelvis/calyces enlargement incidence rate was higher in the ICH subgroup OR 9,17 (95% CI, 2,15-39,06).&#x0D; Conclusions. The obtained data indicate the smaller pole-to-pole dimension of both kidneys in hypertensive subjects who suffered hemorrhagic stroke, accompanying higher incidence rate of kidney calculus formation in view of the increased blood plasma uric acid concentration. The same is typical for the SAH individuals subgroup but with the addition of prevalence of kidney cysts incidence rate. As for the ICH subgroup, in addition to the main group findings, pelvis/calyces enlargement is observed more frequently when comparing to the hypertensive only subjects.

Long-term safety of dietary salt: A 5-year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study).

High-salt diets promote urine dilution and decrease urolithiasis risk. Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). Twenty research colony neutered, healthy aged cats (11.5 years [10.0-11.6], median [interquartile range]). Healthy cats were randomized to control or high-salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2-dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. Follow-up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6-48.2]) and high-salt group (51.4 months [45.7-59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end-diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high-salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years.

The Effect of Sildenafil on Adenine-Induced Chronic Kidney Disease in Mice

This study was done to find the potential renal protective effects of sildenafil and its underlying mechanisms in mice with adenine-induced CKD. For the experiment, 40 male mice were split into four groups. The control group (A) received the same food without medication until the research ends, while the other three collections (B, C, and D) were given adenine (0.25% w/w in feed daily for 8 weeks), groups (C and D) were given sildenafil (0.5 and 2.5 mg/kg) respectively orally every day for 30 days, and then blood samples were taken to assess the function of the kidneys (Urea, total protein, and creatinine), total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) in addition to kidney histopathology, as well as body and kidney weight. Administration of adenine caused weight loss, increased TAC, SOD, and CAT, and increased plasma concentrations of urea, total protein, and creatinine. Damage-related renal histopathological indicators (fibrosis and inflammation) were considerably elevated by adenine. Most of the aforementioned metrics improved with sildenafil, indicating that it might be utilized as an adjuvant treatment for CKD in people through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Yeast polysaccharide supplementation: impact on lactation, growth, immunity, and gut microbiota in Dezhou donkeys.

The Dezhou donkey, a prominent Chinese breed, is known for its remarkable size, rapid growth, and resilience to tough feeding conditions, and disease resistance. These traits are crucial in meeting the growing demand for Ejiao and donkey meat. Yeast polysaccharide (YPS), a functional polysaccharide complex known for its immune-enhancing and growth-promoting properties in livestock and poultry, remains relatively understudied in donkeys. This study aimed to investigate the impact of YPS supplementation on lactating and growing Dezhou donkey jennies and foals. Twelve 45-day-old Dezhou donkey foals and their jennies, matched for body weight and age, were randomly allocated to two dietary groups: a control group receiving a basal diet and an experimental group receiving the basal diet supplemented with 10 g/pen of YPS. The experiment was conducted over a 23-day period, during which donkey foals and lactating jennies were co-housed. The findings revealed that YPS supplementation had no adverse effects on milk production or composition in Dezhou donkey jennies but significantly increased feed intake. Additionally, YPS was associated with increased plasma glucose and creatinine concentrations in foals, while tending to decrease alkaline phosphatase, white blood cell count, red blood cell count, and hemoglobin levels (p < 0.10). Immune indices demonstrated that YPS supplementation elevated the levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) in jennies (p < 0.05) and increased complement component C4 concentrations in foals (p < 0.05). Moreover, YPS positively influenced the fecal microbiome, promoting the abundance of beneficial microorganisms such as Lactobacillus and Prevotella in donkey foals and Terriporobacter and Cellulosilyticum in jennies, all of which contribute to enhanced feed digestion. Additionally, YPS induced alterations in the plasma metabolome for both jennies and foals, with a predominant presence of lipids and lipid-like molecules. Notably, YPS increased the concentrations of specific lipid metabolites, including 13,14-Dihydro PGF2a, 2-Isopropylmalic acid, 2,3-Dinor-TXB2, Triterpenoids, Taurocholic acid, and 3b-Allotetrahydrocortisol, all of which are associated with improved animal growth. In conclusion, this study suggests that dietary supplementation of YPS enhances feed intake, boosts immunity by increasing immunoglobulin levels, stimulates the growth-promoting gut microbiota (Lactobacillus and Prevotella), and exerts no adverse effects on the metabolism of both Dezhou donkey jennies and foals.

Care of the acute kidney injury patient

Acute kidney injury, previously called acute renal failure, indicates a sudden and often reversible reduction in kidney function as measured by glomerular filtration rate, increased serum and plasma creatinine concentration and changes in urine output. This article reviews the pathophysiology and common causes of acute kidney injuries, including pre-renal causes from hypovolaemia, intrinsic renal causes such as glomerular diseases and post-renal obstructive causes. Veterinary nurses should be aware of the common diagnostic tests used and how to deliver support to the hospitalised patient. While an acute kidney injury can be a serious condition for some patients, it is possible for others to recover and maintain a good quality of life with effective nursing care to help maximise the prognosis of these patients.

No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.

Creatine and creatinine quantified using nuclear magnetic resonance: A method validation study and clinical associations between circulating creatine and fatigue in kidney transplant recipients

BackgroundA potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue. MethodsAn NMR assay was developed and validated for measurement of circulating creatinine and creatine concentrations. Plasma creatine and creatinine concentrations were measured in 618 KTR. Fatigue was assessed using the checklist individual strength. Associations of creatine parameters with fatigue was assessed using linear mixed effect models. ResultsThe NMR-based assay had good sensitivity, precision and demonstrated linearity across a large range of values. Among KTR, the mean age was 56 ± 13 years, 62% were men and eGFR was 54 ± 18 ml/min/1.73 m2. Plasma creatine concentration was 27 [19–39] µmol/L. Estimated intramuscular creatine concentration was 27 ± 7 mmol/kg. Higher plasma creatine concentration and higher estimated intramuscular creatine concentration were independently associated with a lower total fatigue score and less motivation problems. ConclusionAn NMR method for measurement of circulating creatine and creatinine which offers the potential for accurate and efficient quantification was developed. The found associations suggest that improving creatine status may play a beneficial role in mitigating fatigue.