Lower Ccr Research Articles

Impact of intra-patient variability of tacrolimus on allograft function and CD4 + /CD8 + ratio in kidney transplant recipients: a retrospective single-center study.

Tacrolimus is a critical component of immunosuppressive therapy for kidney transplant recipients. Intra-patient variation (IPV) of tacrolimus levels affects the function of transplanted kidney. This study aimed to investigate the impact of tacrolimus IPV on kidney function, examine its association with post-transplant duration, and assess its effect on the immune status of transplant recipients. This retrospective study was conducted from January 2016 to February 2022. IPV was evaluated using the coefficient of variation (CV) of tacrolimus trough levels from 6 to 48months after transplantation. Patients were divided into low- and high-IPV groups based on the median CV. Significant differences in kidney function, CD4 + /CD8 + ratio, and post-transplant duration between these groups were analyzed. Among 189 patients, tacrolimus IPV showed a strong correlation with serum creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR) (p < 0.05). Tacrolimus IPV was significantly correlated with post-transplant duration in only two patients (p < 0.05). Using a median CV of 15.4% to categorize patients, the high IPV group, compared to the low IPV group, exhibited significantly higher eGFR at 6-9months (p < 0.05), lower Ccr at 9-12months (p < 0.05), and reduced Ccr and eGFR at 15-18months (p < 0.05). Six months after transplantation, the high IPV group had a significantly lower CD4 + /CD8 + ratio than the low IPV group (p < 0.05). This study highlights the significant impact of tacrolimus IPV on transplant kidney function and immune status in transplant patients at various post-transplantation intervals.

Chill-tolerant Gryllus crickets maintain ion balance at low temperatures

Insect cold tolerance is both phenotypically-plastic and evolutionarily labile, but the mechanisms underlying this variation are uncertain. Chill-susceptible insects lose ion and water homeostasis in the cold, which contributes to the development of injuries and eventually death. We thus hypothesized that more cold-tolerant insects will better maintain ion and water balance at low temperatures. We used rapid cold-hardening (RCH) and cold acclimation to improve cold tolerance of male Gryllus pennsylvanicus, and also compared this species to its cold-tolerant relative (Gryllus veletis). Cold acclimation and RCH decreased the critical thermal minimum (CTmin) and chill coma recovery time (CCR) in G. pennsylvanicus, but while cold acclimation improved survival of 0°C, RCH did not; G. veletis was consistently more cold-tolerant (and had lower CCR and CTmin) than G. pennsylvanicus. During cold exposure, hemolymph water and Na+ migrated to the gut of warm-acclimated G. pennsylvanicus, which increased hemolymph [K+] and decreased muscle K+ equilibrium potentials. By contrast, cold-acclimated G. pennsylvanicus suffered a smaller loss of ion and water homeostasis during cold exposure, and this redistribution did not occur at all in cold-exposed G. veletis. The loss of ion and water balance was similar between RCH and warm-acclimated G. pennsylvanicus, suggesting that different mechanisms underlie decreased CCR and CTmin compared to increased survival at 0°C. We conclude that increased tolerance of chilling is associated with improved maintenance of ion and water homeostasis in the cold, and that this is consistent for both phenotypic plasticity and evolved cold tolerance.

The relationship between obesity and diabetic nephropathy in China

BackgroundThe epidemic of diabetic nephropathy (DN) has been paralleled by rapid increases in both obesity and diabetes in China. The aim of this study was to investigate the natural history of DN and the association of obesity and renal function with diabetes.MethodsIn total, 264 patients with renal biopsy-confirmed DN were examined from 2002 to 2008 and followed up to June 2008 in our institute. Among these, 129 patients were classified into a Kidney Disease Outcomes Quality Initiative (K/DOQI) stage I subgroup. Weight status, clinico-histopathological features, the development of end-stage renal disease (ESRD) and increased proteinuria were evaluated at the baseline of biopsy and during the follow up. Lean, overweight and obese phenotypes were defined as body mass index (BMI) less than 25 kg/m2, 25–28 kg/m2, and more than 28 kg/m2 over, respectively.ResultsIn the patients with renal biopsy-confirmed DN, BMI was 25.5 ± 3.39 kg/m2, with 122 (46.2%), 83 (31.4%) and 59 (22.3%) having lean, overweight and obese phenotypes, respectively. Mean proteinuria was 3.09 ± 2.32 g/24 h, serum creatinine was 2.02 ± 2.02 mg/dL, and creatinine clearance rate (Ccr) was 96.0 ± 54.0 mL/min/1.73 m2. Compared with obese patients, lean patients had a lower Ccr, a higher percentage of anemia, more renal lesions and higher risk for ESRD (HR = 1.812, P = 0.048). The weight in obese patients decreased significantly after 27 months, and lean patients had a longer duration of diabetes than obese patients. Regarding patients at K/DOQI stage I, patients with DN showed similar duration of diabetes regardless of weight status. Minimal weight loss was recorded in obese patients during follow-up, and they exhibited greater glomerular hyperfiltration and higher risk for increased proteinuria (HR = 2.872, P = 0.014) than lean patients.ConclusionsIn China, obesity is common in DN patients undergoing biopsy. Initial high levels of proteinuria and subsequent weight loss are the major characteristics of the natural course of DN. Obesity contributed to increased proteinuria at an early stage, while the lean phenotype was associated with ESRD development, especially at the later stages.

Incidence and risk factors of renal dysfunction after liver transplantation in Korea

Renal dysfunction, one of the most common complications after liver transplantation, influences patient outcomes. Little is known, however, about it in Korea. The aims of this study were to determine the incidence and to identify the risk factors for renal dysfunction after liver transplantation. Sixty-two patients who survived over 6 months after transplantation were enrolled. Renal function was classified by creatinine clearance (Ccr, mL/min), which was estimated using the Cockcroft-Gault formula. Twenty-seven patients (44%) showed mild renal dysfunction (60 ≤ Ccr < 90), and 27 patients (44%), moderate dysfunction (30 ≤ Ccr < 60). The others were found to have normal function (Ccr ≥ 90). None displayed severe dysfunction (Ccr < 30). Compared to a control group (Ccr ≥ 60), the renal dysfunction group showed lower preoperative Ccr (91 ± 28.6, 63 ± 21.9, respectively, P < .01) and lower Ccr at 3 months after transplantation (72 ± 17.1, 49 ± 14.6, respectively, P < .05). Age, sex, immunosuppressive drug usage, serum tacrolimus levels, and the frequency of postoperative acute renal failure did not affect the postoperative renal dysfunction. Twenty-six patients received mycophenolate mofetil while reducing the dose of calcineurin inhibitors because of compromised renal function. With mycophenolate mofetil treatment, the renal function seemed to improve, although the difference was not statistically significant ( P = .057). These data demonstrate that renal dysfunction is common after liver transplantation and that preoperative renal function is the important factor predicting postoperative renal dysfunction.

Community‐based study in Taiwan aborigines concerning renal dysfunction in gout patients

Objective: To reveal the factors associated with renal dysfunction among gout patients in Taiwan aborigines.Methods: Social demographic data, alcohol consumption data, anthropometric measurements, blood samples, and 24‐h urine samples were collected from 128 aboriginals (101 men, 27 women) suffering from gout.Results: The men displayed higher mean creatinine clearance (Ccr) values than women. Twenty‐two post‐menopausal women had significantly lower Ccr values compared to the five pre‐menopausal women [probability (p)<0.001]. The males displayed higher 24‐h urinary creatinine value than females (8.60±5.39 versus 5.58±2.14 mmol/L; p<0.05), and showed a significantly higher positive relationship between 24‐h urinary creatinine and uric acid excretion [correlation coefficient (r)=0.7304; p<0.001], whereas the females did not (r=0.1144; p=0.5691). Overall, those who were older members of the Tsou tribe, or had excreted less uric acid from urine in 24 h tended to suffer renal dysfunction.Conclusions: Gout patients displayed diversity in renal function. An exogenous source of creatinine in men was more likely than in women.

Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population.

Microalbuminuria (MA) is an important early sign of diabetic nephropathy. Hyperfiltration and impaired filtration in relation to albuminuria has been well investigated in diabetic subjects. This study tested the hypothesis that an increased urinary albumin excretion (UAE) is associated with renal functional abnormalities also in nondiabetic subjects. The relation between UAE and creatinine clearances (Ccr) in 7728 nondiabetic subjects was studied. Subjects were divided in four groups according to UAE (mg/24 h): 0 to 15 (control), 15 to 30 (high-normal albuminuria [HNA]), 30 to 300 (MA), >300 (macroalbuminuria). An elevated filtration and a diminished filtration were defined as a Ccr exceeding or below 2x the SD of the control group corrected for age and gender. Ccr followed a parabolic trend, with a higher Ccr in the HNA as compared with control and a lower Ccr in the MA and macroalbuminuria group as compared with HNA. With each increasing UAE level, male sex, age, body mass index, minimal waist circumference, systolic and diastolic BP, plasma glucose, and a positive family history for diabetes all followed a significant linear increasing trend (P < 0.001). After adjustment for age, gender, body mass index, plasma glucose, a positive family history for diabetes, systolic and diastolic BP, antihypertensive medication, and smoking in a multivariate analysis, HNA and MA were independently associated with an elevated filtration (RR 1.8 [95% confidence interval, 1.30 to 2.51] and 1.7 [1.17 to 2. 45]). Macroalbuminuria was independently associated with a diminished filtration (4.3 [range, 1.97 to 9.36]). In conclusion, an elevated UAE might be an important and early sign for progressive renal function loss in a nondiabetic population.

ＫＷ‐４６７９の高齢者における体内動態試験 単回および反復投与時の体内動態

We evaluated the pharmacokinetics of KW-4679, a new antiallergic agent, in the elderly in single dosing and repeated dosing trials. In, the single dosing trial, the pharmacokinetics of a single dose of 10 mg KW-4679 in elderly male subjects [74±2yrs (mean±SD), n=6] were compared with these in young male subjects (21±1yrs, n=6). In the repeated dosing trial for 6 consecutive days, the pharmacokinetics of the last administration of 10 mg KW-4679 were compared with those of the first administration in elderly male subjects (74±3 yrs, n=6) to determine the accumulation of KW-4679 and/or its metabolites. In the single dosing trial, Cmaxand AUCin the elderly subjects were significantly larger than in the young subjects, while Cl/F was significantly smaller in the elderly subjects. There was no significant difference in the fraction of KW-4679 excreted in the urine between the elderly and the young subjects (69.3 ± 6.3% and 62.5±5.4% in the young and the elderly subjects, respectively). ClR in the elderly subjects (7.52 ± 2.18 L/hr) was significantly smaller than that in the young subjects (14.4± 2.20 L/hr). Although ClR was, correlated with Ccr, ClR was significantly larger than Ccr, implying that this agent undergoes renal tubular secretion. In the repeated dosing trial, all pharmacokinetic parameters examined, except for Cmax, showed no difference between the first and the last administration.The accumulation of KW-4679 and/or its metabolites could not be detected in the elderly subjects examined in the repeated dosing trial for 6 days, though these results suggested that the dose should be reduced in the elderly subjects who have lower Ccr.

Effect of Long-Term Low-Dose Aluminum-Containing Agents on Hemoglobin Synthesis in Patients with Chronic Renal Insufficiency

To investigate the possible toxic effects of long-term low-dose exposure to A1-containing agents in 55 patients with chronic renal insufficiency (CRI), 37 patients received A1(OH)3 1 tablet 3 times per day (about 302 mg/day of elemental A1) for 3 months and another 18 were used as a control group. The hematological, iron status and A1 data were measured before and after the study. CRI patients who had ingested A1-containing agents for 3 months had significant decreases in hematological parameters and increases in serum A1 and daily urinary A1 excretion. Serum ferritin negatively correlated with serum A1 (r = -0.586, p < 0.0005), and hemoglobin (Hb) positively correlated with renal A1 clearance (r = 0.573, p < 0.0005) and logarithmic transformation of serum A1 (r = -0.437, p < 0.01) in these patients, despite no significant correlations between initially basal hematological and A1 parameters. But there were no significant differences between variables of A1 and hematological parameters before and after 3 months of follow-up in the control group. All factors correlating with Hb were measured with stepwise regression analysis; renal A1 clearance, creatinine clearance (Ccr) and serum iron were the most significant correlation factors with Hb. After Ccr and serum iron had been adjusted, Hb (b = 0.069 +/- 0.02; p < 0.05) still positively correlated with renal A1 clearance. Comparing patients who had reduced Hb (at least 0.5 g/dl) and those who did not, the response group had a lower basal (Ccr, a higher serum A1 and a lower renal A1 clearance after A1 loading for 3 months. In conclusion, A1 does play a role in the significant reduction of Hb and hematocrit in CRI patients after A1 loading for 3 months, and patients with a lower Ccr may easily develop A1-induced hematologically toxic effects. A1-containing agents should be used with care in long-term therapies of CRI patients.