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The effect of short-term glucagon infusion on kidney function in normal man.

Kidney function was studied in six normal males before and during a 2 h glucagon (10 ng/kg/min) infusion. The following variables were determined during each 20 min clearance period; glomerular filtration rate (GFR), renal plasma-flow (RPF) , filtration fraction (FF), urinary albumin and beta2-microglobulin-excretion rates. Glucagon infusion resulted in a fourfold increase in plasma glucagon concentration. The infusion induced a significant increase in GFR (+9%), FF (+9%) and urinary beta2-microglobulin excretion rate (+32%), (p less than 0.01). RPF and urinary albumin excretion rates were not significantly changed. We suggest that glucagon may contribute to the reversible kidney function alterations typically found in poorly regulated juvenile diabetes, a state with relative or absolute hyperglucagonaemia.

Adult

[Hypothermic storage under aerobic conditions--the effect of different flushing solutions on kidney functional recovery].

Canine kidneys (n = 17) were flushed with COLLINS (C2), SACKS II, LAMBOTTE (KMgS), ROSS (hypertonic citrate), or RINGER glucose-mannitol solution following a 30-min period of normothermic ischemia. After 24 h hypothermic preservation with retrograde oxygen persufflation (ROP) and autotransplantation, the immediate functional recovery was determined using inulin and PAH clearance methods and compared with the normal contralateral kidney. While a good functional recovery was found in the COLLINS group, significantly exceeding results from hypothermic ischemic storage preservation, in experiments using other flush solutions ROP preservation resulted in only a small immediate function. Thus the experiments indicate that COLLINS solution C2 is the optimal flush solution for ROP preservation.

Aerobiosis

Identification of Genetic Variations in HLA Region for Kidney Functions.

HLA allelic polymorphisms are associated with a variety of kidney-related traits in different populations. Although Taiwanese-specific genetic variants associated with kidney function have been reported, the role of HLA alleles is unclear. In this study, the association between eGFR and genetic variations in the HLA region was explored in a cohort of 59,448 Taiwanese subjects. A total of 448 genetic variations in the HLA region are significantly associated with eGFR. HLA-C*03 is associated with decreased eGFR, while HLA-DQA1*03, HLA-DQB1*03:03 and HLA-DQB1*03:03:02 demonstrated protective effects. Moreover, amino acid changes on HLA-C and HLA-DRB1 are significantly associated with eGFR. Finally, the eGFR-associated single nucleotide variations (SNVs) and insertions and deletions (indels) are enriched in the HLA-DQB1 gene. After conditional analysis, we identified two independent signals, including rs2853941, rs3830060. In summary, this study highlights the role of HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 variations in kidney function in the Taiwan Han Chinese population.

Adult

The interplay between impaired kidney function and hypertension in dementia: A 13-year longitudinal study.

BackgroundHypertension and kidney function impairment (KFI) are established risk factors for dementia and may reinforce each other. However, whether their coexistence confers excess dementia risk remains unclear.ObjectiveTo examine the multiplicative and additive interactions between hypertension and KFI in relation to incident dementia and explore potential biological pathways.MethodsWe included 218,858 dementia-free adults followed for a mean of 13.2 years. KFI was defined as an estimated glomerular filtration rate <60&#x2005;mL/min/1.73&#x2005;m2. Cox proportional hazards models assessed independent associations and multiplicative interaction, while additive interaction was evaluated using the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Plasma proteomic data on 2911 proteins were available for 6127 participants.ResultsHypertension was associated with dementia risk (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.17-1.31; p&#x2009;<&#x2009;0.001), whereas KFI was not (HR, 1.02; 95% CI, 0.94-1.11; p&#x2009;=&#x2009;0.571). A significant multiplicative interaction was observed (p&#x2009;=&#x2009;0.018). KFI was associated with dementia only among participants with hypertension (HR, 1.15; 95% CI, 1.01-1.29; p&#x2009;=&#x2009;0.023). A positive additive interaction was also observed (RERI, 0.27; 95% CI, 0.05-0.49; AP, 0.17; 95% CI, 0.05-0.29; SI, 1.84; 95% CI, 1.11-3.07), although it was attenuated after full adjustment. Proteomic analyses implicated immune and inflammatory pathways.ConclusionsHypertension may modify the association between impaired kidney function and dementia risk. Their coexistence may identify individuals at higher risk, but further studies are needed to confirm these findings and clarify the underlying mechanisms.

Humans

[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation].

Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).

Adult

Efficacy and safety of revascularization in patients with chronic limb-threatening ischemia by kidney function.

BACKGROUND: The optimal revascularization strategy for patients with chronic limb-threatening ischemia (CLTI) with chronic kidney disease (CKD) remains unknown. We evaluated whether the efficacy and safety of surgical vs endovascular revascularization differ by kidney function. METHODS: In this post hoc secondary analysis of BEST-CLI trial (NCT02060630), 1,704 patients with CLTI were stratified by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m&#xb2;): non-CKD (eGFR &#x2265; 90), mild-moderate CKD (eGFR 45-89), advanced CKD (eGFR < 45 or dialysis). The primary outcome was a composite of major adverse limb events (MALE) or death. We estimated the difference in restricted mean time lost (RMTL, in days) adjusted for inverse probability treatment weights. RESULTS: Surgical revascularization was significantly associated with fewer days with MALE or death in non-CKD (RMTL difference: -127.8 days; 95% CI -176.1, -79.6) and mild-moderate CKD (-63.2 days; 95% CI -104.7, -21.8) but not in advanced CKD (-16.4 days; 95% CI -78.8, 46.0; P interaction = .02). This attenuation reflected a diminishing mortality benefit with more severe CKD (P interaction = .01), whereas the association with fewer days with MALE remained consistent across CKD strata (P interaction = .34). Major adverse cardiovascular events and serious adverse events were more common with more severe CKD but did not differ significantly by treatment. CONCLUSIONS: Surgical vs endovascular revascularization was consistently associated with fewer days with MALE across CKD strata. However, its association with mortality varied by kidney function, attenuating the overall benefit for the composite endpoint of MALE or death. These results support individualized revascularization strategies, but require prospective confirmation. TRIAL REGISTRATION: The BEST CLI trial is registered at ClinicalTrials.gov (NCT02060630).

Humans

[Kidney functional dynamics in eliminating vasorenal hypertension by a kidney autograft].

In acute and chronic experiments on 45 dogs the authors obtained vasorenal hypertension, the elimination of which was fulfilled by means of autotransplantation of the kidney without transection of the ureter. The dynamical study of renal function was carried out through an analysis of arterial blood pressure, erythropoietic activity, blood serum, reticulocytic count, creatinine, residual nitrogen, diuresis, radioisotopic investigation, chromocystoscopy at open bladder, excretory urography, aortograhy, phlebography and morphometric studies of the renal glomeruli.

Animals

[Concentration of C-peptide in correlation to kidney function (author's transl)].

Recently, the radioimmunological determination of C-peptide came into interest because of the jugdement of the remaining function of the islet apparatus in insulin-dependent diabetics. As the degradation of C-peptide preferably takes place in the kidney we performed an intravenous glucose load in 32 patients with kidney diseases. The following results were obtained: 1. In patients with a healthy carbohydrate metabolism a clear correlation exists between the concentration of creatinine on the one hand, the creatinine-clearance and the fasting C-peptide concentration respectively the measured amount of C-peptide on the other hand. 2. The more advanced the renal insufficiency the better is the correlation between the parameter of the kidney function and the C-peptide concentration. 3. In diabetic patients there shows to be no clear correlation between the C-peptide levels and the kidney function. --In insulin-dependent diabetics the amount of C-peptide is only of diagnostic use if the renal function is well known.

Adult

Finerenone and Cardiovascular Outcomes According to Baseline Kidney Function in Patients With Heart Failure: The FINEARTS-HF Trial.

BACKGROUND: Finerenone is known to reduce the risk of worsening heart failure (HF) events and cardiovascular (CV) death in patients with HF with mildly reduced or preserved ejection fraction. OBJECTIVES: The authors explored whether the benefit of finerenone among patients with HF with mildly reduced or preserved ejection fraction differs according to baseline measures of kidney function. METHODS: FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a global, randomized clinical trial of finerenone vs placebo among patients with HF with mildly reduced or preserved ejection fraction. Finerenone was titrated to 20 mg/d if the estimated glomerular filtration rate (eGFR) was &#x2264;60 mL/min/1.73 m2 or 40 mg/d if eGFR was >60 mL/min/1.73 m2. The authors used a semiparametric proportional rates method, stratified by left ventricular ejection fraction (<60%; &#x2265;60%) and region, to assess for differential treatment effects on the composite of total HF events and CV death according to the baseline eGFR (continuous and categories [&#x2265;60 mL/min/1.73 m2, 45 to <60 mL/min/1.73 m2, <45 mL/min/1.73 m2] and urine albumin-creatinine ratio (UACR) (<30 mg/g, 30 to <300 mg/g, &#x2265;300 mg/g). RESULTS: The effect of finerenone to reduce the primary endpoint of total HF events and CV death did not significantly differ according to baseline eGFR (Pinteraction = 0.14 and 0.07 for continuous and categorical eGFR, respectively) with rate ratio 0.72 (95% CI: 0.59-0.88) for eGFR &#x2265;60 mL/min/1.73 m2, 0.83 (95% CI: 0.65-1.06) for eGFR 45 to <60 mL/min/1.73 m2, and 1.02 (95% CI: 0.83-1.26) for eGFR <45 mL/min/1.73 m2. The corresponding absolute event rates were 9.2 vs 12.5, 16.5 vs 19.9, and 28.0 vs 28.0 per 100 patient-years for finerenone vs placebo, respectively. Similar results were noted for total worsening HF events. Finerenone lowered the risk of the composite CV outcome similarly across baseline categories of UACR (Pinteraction = 0.48). CONCLUSIONS: In the FINEARTS-HF trial (where the target dose of finerenone was determined by baseline kidney function), the effect of finerenone to reduce the composite of cardiovascular death and total HF events did not significantly differ across a range of baseline eGFR and UACR.

Humans

[Animal experimental studies on partial kidney function after temporary tourniquet ischemia with and without blood substitute therapy].

70 rats were subjected to tourniquet ischemia of a hind limb for a period of two and three hours. 12 rats served as controls. After release of the 3 hours tourniquets 20 rats were treated either with Ringer's solution or with hydroxyethyl starch. Kidney function and morphology, systolic blood pressure, hematocrit, serum electrolytes, creatinine and urea were studied as different times of recirculation. 1. Reduction in renal function was only observed after releasing the tourniquets. 2. The extent of reduction in renal function depended on the time of ischemia and time of recirculation. 3 hours of tourniquet with two hours of recirculation led to the largest extent of reduction in renal function and renal parenchymal lesions. 3. If the infusion of HES was applied at the beginning of recirculation, reduction in renal function was prevented, as well as parenchymal lesions. Ringer's infusion, however, did not improve kidney function to a normal range.

Animals

Percutaneous transluminal angioplasty for renal artery stenosis in a solitary functioning kidney.

In five patients with hypertension and marked impairment of renal function due to renal artery stenosis in a solitary functioning kidney, a nonsurgical technique, percutaneous transluminal angioplasty, was used to dilate the stenotic renal artery. Blood pressure improved in all five patients, and renal function improved in three. One patient subsequently died of multiple cardiovascular complications, and in one patient the procedure resulted in acute renal failure requiring hemodialysis. Although preliminary, this experience suggests that percutaneous transluminal angioplasty may provide an attractive alternative to surgery in severely ill patients at high surgical risk.

Aged

Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate.

A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.

Animals

Kidney function in normal man during short-term growth hormone infusion.

Kidney function was studied in 9 normal males before and during a 2 h growth hormone (GH) infusion of 50 ng/kg/min. The following variables were measured during each 20 min clearance period: glomerular filtration rate, GFR, effective renal plasma flow, RPF (steady state infusion technique with urinary collections using [125I]iothalamate and [131I]iodohippurate), and urinary albumin and beta2-microglobulin excretion rates (radioimmunoassays). The GH infusion resulted in a 10-fold increase in plasma GH concentration. All the above mentioned variables remained practically unchanged during the infusion except for a small (-5%) but significant decrease in renal plasma flow (P less than 0.01). Our negative results contrast to the findings of increased GFR and RPF during prolonged GH administration and suggest that GH requires several hours or days for its renal effects to become manifest.

Adult

[The influence of hydroxyethyl starch solutions on circulation and on kidney function in hypovolaemic patients (author's transl)].

In a group of 12 hypovolemic patients some parameters of circulation and kidney function were measured before and after an infusion of 1000 ml 6% hydroxyethyl starch solution (HES) was given. There were found increases in cardiac output, centralvenous pressure and endogenous creatinine clearance, and decreases of total peripheral resistance and shock index. Under the conditions of this investigation HES solution showed good properties as a plasma substitute.

Blood Circulation

Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.

Animals