Severe hyponatraemia and hypouricaemia in Gitelman's syndrome.
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Adult↗
Biomedical subjects
N Lameire
Publications and source records attributed to N Lameire.
The anti-proliferative effect of calcitriol on HL-60 cells is neutralized by uraemic biological fluids.
BACKGROUND: It has been demonstrated that uraemic serum/ultrafiltrate inhibits cell-mediated immune response in vitro, and that it suppresses calcitriol synthesis and its biological actions. METHODS: In the present in vitro study, the effect of calcitriol, uraemic ultrafiltrate (UUF) and a combination of both on the human promyelocytic leukaemia cell line, HL-60, was studied by evaluating bromodeoxyuridine (BrdU) incorporation into the DNA, luminol-amplified chemiluminescence (CL) production, expression of CD14, and levels of vitamin D receptor mRNA (VDR mRNA) and CD14 mRNA. RESULTS: The ability of calcitriol to block cell proliferation (37.4+/-5.4 to 30.5+/-5.6% cells incorporating BrdU, P:<0.01) was neutralized when UUF was applied together with calcitriol (53.4+/-21.3% cells incorporating BrdU, P:<0.01 vs calcitriol alone). Similarly to what was observed for BrdU incorporation, the CL production of HL-60 cells was enhanced in the presence of calcitriol (20126+/-10154 to 61528+/-24021 cpm, P:<0.01), and was suppressed again in the presence of calcitriol and UUF (20916+/-12075 cpm, P:<0.01 vs calcitriol alone); finally UUF also inhibited the calcitriol-induced CD14 expression (71.1+/-11.2 to 54.9+/-17.7% CD14 positive cells, P:<0.05). On the other hand, the calcitriol-induced CD14 mRNA levels were not significantly different in the presence of calcitriol and UUF compared to calcitriol alone. This points to an inhibition by UUF at a post-transcriptional level. Similar data were found for VDR mRNA levels. UUF was fractionated by HPLC in four fractions, hydrophilic uraemic solutes being eluted first (F1) and hydrophobic solutes being eluted last (F4); fractions 1, 2 and 3 simultaneously affected both BrdU incorporation and CL production in a significant way. CONCLUSIONS: It is concluded that UUF contains factors that impair calcitriol-activated function of HL-60 cells. Hence, the differentiation and immune response of these promyelocytic leukaemia cells, as induced by the supplementation of calcitriol, is neutralized in the presence of uraemic biological fluids. This may be of relevance for the propensity to infection and malignancy of the uraemic patient.
Biological Factors↗
Relationship between gastric emptying and clinical and biochemical factors in chronic haemodialysis patients.
BACKGROUND: Gastroparesis is an important side-effect of end-stage renal disease because of its influence on nutritional status. METHODS: In this study, 56 equilibrated haemodialysis patients were evaluated by radioisotopic examination for gastric emptying time. These data were correlated to anthropometrical as well as biochemical parameters. RESULTS: The half-life time for gastric emptying was 83+/-34 min in the overall population, compared to 50+/-15 min in a normal reference population. Prealbumin, mean fibular nerve-conduction velocity and intra- as well as extracorpuscular folic acid were significantly different between patients with the lowest and highest gastric emptying times. Linear correlation analysis between the half-life for residual radioactivity and the remaining parameters yielded a significant correlation for blood urea nitrogen, serum folic acid, intracorpuscular folic acid, serum vitamin B(12), serum C-reactive protein, serum prealbumin and mean fibular nerve-conduction velocity. CONCLUSIONS: This study demonstrates that gastric emptying is significantly delayed in end-stage renal disease patients. The delay is associated with changes in biochemical indicators of nutritional status such as serum albumin and prealbumin.
Aged↗
Selected practical aspects of intermittent hemodialysis in acute renal failure patients.
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Acute Kidney Injury↗
Pathophysiologic features and prevention of human and experimental acute tubular necrosis.
Acute renal failure (ARF) remains a common and potentially devastating disorder that affects as many as 5% of all hospitalized patients, with a higher prevalence in patients in critical care units. The focus of this article is on categorizing recent pathophysiologic and clinically relevant developments in the field. The vascular and tubular factors in the pathogenesis of ARF, together with the potential mechanisms of recovery and repair of the injured kidney, are discussed. A number of experimental and clinical interventions to prevent. ARF are summarized. Although the clinical treatment of these patients is still largely supportive and many recent clinical trials showed rather negative results, it is hoped that basic research will provide therapeutic tools to improve the grim prognosis of this disease in the future.
Animals↗
What is the renal replacement method of first choice for intensive care patients?
Renal replacement therapy for the patient with acute renal failure on the intensive care unit can be offered in several different formats: intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), and slow low-efficient daily dialysis (SLEDD). It is frequently claimed that CRRT offers several advantages over IHD, but most of these, such as correction of metabolic acidosis, better recovery of renal function, better clinical outcome due to application of biocompatible dialysis membranes, correction of malnutrition, and better removal of cytokines, are not corroborated by the results of controlled prospective studies. There is also no evidence that CRRT results in a better survival, compared with IHD. The only potential advantages of CRRT that stood the test of clinical evaluation (hemodynamic stability, correction of hypervolemia, better solute removal) can be offered as well by SLEDD. In addition, the latter strategy is less expensive because the same infrastructure is used as for IHD, while the patient is not immobilized continuously, which leaves time free for other activities such as nursing care and technical investigations. SLEDD is a relatively young technique, so thorough clinical studies are lacking. Nevertheless, the hypothesis is proposed that SLEDD offers a valuable alternative to the classical dialysis strategies, applied in the intensive care patient.
Acute Kidney Injury↗
Mimicry of surreptitious diuretic ingestion and the ability to make a genetic diagnosis.
Gitelman's syndrome, also known as "hypocalciuric variant of Bartter's syndrome", is a cause of chronic hypokalemia and hypomagnesemia in adults. A specific gene has been found responsible for this disorder, encoding the thiazide-sensitive NaCl coporter (TSC) in the distal convoluted tubule. We describe a psychiatric patient with chronic symptomatic hypokalemia and hypomagnesemia whose electrolyte disturbances were subsequently misdiagnosed as an acute alcohol and benzodiazepine withdrawal syndrome, as chronic diuretic abuse and as a classical Bartter's syndrome. Finally, genetic investigation revealed the presence of mutations in the SLC12A3 gene leading to the proper diagnosis of Gitelman's syndrome. We emphasize that Gitelman's syndrome should be suspected in every hypokalemic patient with biochemical resemblance of diuretic ingestion, especially when repeated toxic screens for diuretics are negative. The ability to make a molecular-genetic diagnosis can be of practical benefit in confusing clinical settings.
Adult↗
Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact.
BACKGROUND: Several studies have pointed to a release of drugs or protein-bound solutes from their binding sites during heparinization. The effect is attributed to the metabolism of triglycerides to free fatty acids (FFAs), which compete with drugs for protein binding sites. This study evaluated the impact of intradialytic heparin on the free concentration of the uremic toxin p-cresol and on FFAS: METHODS: Blood samples from hemodialysis (HD) patients, before and during HD, were collected with selected anticoagulation strategies. We assessed the effects of standing time, temperature, pH, and the addition of a lipase inhibitor, tetrahydrolipstatin (THL) to blood samples on the free p-cresol concentration. p-Cresol was analyzed by HPLC with fluorescence detection. We measured FFAs by gas chromatography, and the free fractions of added valproic acid and phenytoin were evaluated by fluorescence polarization immunoassay. RESULTS: In blood samples (n = 22) not submitted to a specific treatment, free p-cresol increased from 9.9 +/- 5.1 to 31.9 +/- 22.3 micromol/L after 30 min of heparin HD (P < 0.001) and correlated significantly with FFAs (r = 0.80; P = 0.002; n = 12). There was no increase in free p-cresol during heparin-free HD (n = 6) and trisodium citrate HD (n = 9). In addition, p-cresol in ultrafiltrates (n = 3) did not correspond to the free p-cresol in heparinized blood, suggesting that the increase in free p-cresol was artifactual. The release of p-cresol in the test tube was enhanced by standing time (n = 6), sample temperature (n = 6), and alkaline pH (n = 6). Inhibition of lipase activity with THL prevented the increase of FFAs (n = 6) and the release of free p-cresol during HD (n = 22). These results were corroborated by the study of the free fraction of valproic acid (n = 6) and phenytoin (n = 6). CONCLUSIONS: The free concentrations of protein-bound solutes in plasma of heparinized patients are influenced by external factors that alter the lipase activity in the test tube. The free fraction does not increase during HD when lipase activity is neutralized at the time of blood sampling, so that previously reported increases are probably artifacts.
Aged↗
Advanced glycation end products: specific fluorescence changes of pentosidine-like compounds during short daily hemodialysis.
BACKGROUND: Advanced glycation end products (AGE) accumulate in uremia and represent an important etiopathogenetic cause of morbidity in dialyzed patients. Conventional hemodialysis treatment seems to be ineffective in lowering AGE levels. We wished to investigate whether daily hemodialysis (DHD), a treatment that seems to result in better clinical condition in end-stage renal disease patients, is effective in the reduction of these compounds. METHODS: We evaluated 10 non-diabetic patients on standard hemodialysis (SHD = 3 x 4 h/week) for more than 6 months by a crossover study. These patients were assigned randomly to 6 months of DHD (6 x 2 h/week) or 6 months of SHD. Then, they were switched to 6 months of the alternative treatment. At the end of these two periods, we studied pentosidine-like AGE compounds by measuring the total fluorescence at a wavelength characteristic for these substances: Ex: 335nm/Em:385nm; we also measured protein-linked pentosidine at the same time points. Finally, we determined the AGE-related total fluorescence in the deproteinized serum of 13 uremic patients on peritoneal dialysis (CAPD) and of 10 healthy controls. RESULTS: Pre-HD AGE-related total fluorescence obtained after 6 months of DHD was significantly lower than that obtained with standard HD (DHD = 201.3 +/- 36.4 AU/ml vs. SHD = 267.5 +/- 141.4 AU/ml, p = 0.03). The extraction rate per minute of dialysis was slightly, but not significantly higher during DHD than SHD (0.29 +/- 0.11% vs. 0.23 +/- 0.04, p = 0.07). AGE-related total fluorescence pre-HD values in patients treated by SHD and DHD were about 20-fold higher than in control subjects. They did not differ from CAPD patients. The pre-dialysis level of protein-linked pentosidine was significantly lower in DHD than in SHD (DHD = 16.12 +/- 4.71 pmol/mg protein, SHD = 22.64 +/- 6.86 pmol/mg protein, p < 0.01). CONCLUSIONS: DHD showed a reduction in AGE-related total fluorescence, although the mean value remained higher than in control subjects. DHD is also accompanied by a decrease in protein-linked pentosidine.
Arginine↗
An integrated approach to end-stage renal disease.
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Delivery of Health Care, Integrated↗
Dyspepsia and gastric emptying in chronic renal failure patients.
AIMS: Chronic renal failure (CRF) patients frequently suffer from dyspeptic complaints such as nausea, vomiting, abdominal distension, early satiety and anorexia. The aim of the present study was to define the prevalence of dyspeptic complaints and delayed gastric emptying in CRF patients. MATERIAL AND METHODS: Dyspeptic complaints were assessed anamnestically in 62 non-dialyzed CRF patients. Gastric emptying for solids was evaluated by the 13C-octanoic acid breath test in the same population. The CRF patients were compared to 27 healthy volunteers. RESULTS: There was a high prevalence (48%) of dysmotility-like dyspepsia in the investigated population. The gastric emptying rates of CRF patients and healthy volunteers were significantly different (median gastric emptying t(1/2) 83 min versus 60 min, p < 0.01). Diabetic CRF patients had lower gastric emptying rates than non-diabetic CRF patients (median gastric emptying time t(1/2) 113 min versus 77 min, p < 0.01). Even the non-diabetic CRF patients had a significantly delayed gastric emptying rate compared to the healthy volunteers (77 min versus 60 min, p < 0.05). CONCLUSION: It is concluded that dysmotility-like dyspeptic complaints and delayed gastric emptying are highly prevalent in CRF patients.
Adolescent↗
Integrated care.
The integrated care model for delivering RRT offers apparent advantages in patient choice, optimal survival, and economical use of resources. Dialysis and transplantation have always been used that way; but, by integrating all three treatments--HD, PD, and transplantation--the options for the multi-professional team and the patients are increased. The practical implications of the approach include the need for all treatments to be available, for patients and professionals to be educated in the approach, and for a change in therapy to be anticipated and accepted, not seen as a mark of treatment failure. Prospective studies are needed to quantify the benefits in a more systematic way.
Humans↗
Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis.
BACKGROUND: Delayed graft function (DGF) and acute renal failure (ARF) after renal transplantation negatively influence short- and long-term graft outcome. Peritoneal dialysis as pretransplantation dialysis modality was reported to influence favorably the recovery of renal function immediately after kidney transplantation. It has been hypothesized that fluid status was the factor explaining this better outcome. This hypothesis was tested in this study by multivariate analysis, also including other factors related to DGF and ARF. METHODS: The records of peritoneal dialysis (PD; n=40) and hemodialysis (HD; n=79) patients receiving a first cadaveric kidney transplantation at the University Hospital Gent were analyzed. RESULTS: DGF and ARF were observed in 33 (27 HD and 6 PD, P=0.03) and 14 (14 HD and 0 PD, P=0.01) patients, respectively. The number of days needed to reach a serum creatinine 50% below that before transplantation (T1/2(SCr)), was correlated with cold ischemia time (CIT) (P<0.001) and body weight gain (BWG) (P<0.01) and was inversely correlated with urinary output in the first 24 hr (P<0.001), fluid load (P<0.001), and central venous pressure (P<0.001). A multivariate model with CIT (P<0.001), PD as pretransplantation dialysis mode (P=0.01), urinary output in the first 24 hr (P=0.001), BWG (P=0.05), and fluid load (P=0.01) resulted in an R2 of 0.32 (P<0.001). Using Cox regression analysis, the relative risk for a prolonged T1/2(SCr) increased with 4%/hr CIT (P=0.01) and with 1%/kg BWG (P=0.02). Fluid load decreased the relative risk with 5%/liter (P<0.001) and PD as pretransplantation modality favorably modified the relative risk by a factor of 1.6 (P=0.01). CONCLUSION: PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.
Acute Kidney Injury↗
Arterial reconstruction in hepatic and pancreatic allograft transplantation following multi-organ procurement.
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Arteries↗
55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study.
The feasibility of imaging renal function with 55Co-ethylene diamine tetraacetic acid (EDTA) and dynamic positron emission tomography was investigated. A group of normal Wistar rats was injected intravenously with 55Co-EDTA and underwent dynamic positron emission tomography (PET) imaging in order to study the biodistribution. The time-activity curves of the heart (blood pool), both kidneys, liver, and bladder were observed. In two animals, blood and urinary clearances of 55Co-EDTA were compared with those for 51Cr-EDTA. In one animal, unilateral reduction in kidney function was induced and the right/left ratio for the kidneys was determined. The time-activity curves showed that 55Co-EDTA cleared rapidly from the blood pool (heart), whereas prompt and high target-to-background ratios for both kidneys were obtained. The entire tracer was cleared from the renal parenchyma by urinary excretion and collection of the activity in the bladder. No specific activity uptake was noticed in any other organ or tissue. The clearances of 55Co-EDTA and 51Cr-EDTA in blood were not significantly different, showing that the nature of the M++ has no influence on the in vivo behavior of EDTA. 55Co can be produced easily by cyclotron irradiation and 55Co-EDTA is a promising physiological tracer for nephrological research using PET.
Animals↗
A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas-kidney transplants.
UNLABELLED: Acute rejection remains a major problem in simultaneous pancreas-kidney (SPK) transplant and occurs in 60-100% of the cases. With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving antithymocyte globulin (ATG) or Basiliximab induction therapy and cyclosporine Neoral (CyA), MMF, steroid basis immunosuppression. Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean +/- standard deviation (SD) age of 42 +/- 6 yr. Of these, 14 patients were treated with anti-thymocyte globulin (ATG) Fresenius (rabbit) 3-5 mg/kg for 6 +/- 2 d, cyclosporine Neoral (CyA) (trough levels 350-400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect, Novartis 20 mg on d 0 and d 4 post-transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean +/- SD cold ischemia time (CIT) of the organs was 10.1 +/- 2.4 h for the pancreas and 10.5 +/- 2.6 h for the kidney. RESULTS: Biopsy-proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6-d course of anti-CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA1C) of 5.1 +/- 0.7%, and serum creatinine with a mean of 1.24 +/- 0.24 mg/dL in a mean follow-up period of 17 +/- 15 months (median 12, range 2 37). CONCLUSION: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas-kidney transplant (PKT) with a marked reduction in the incidence of rejection.
Adult↗
A specific method for measurement of nitric oxide synthase enzymatic activity in peritoneal biopsies.
UNLABELLED: A specific method for measurement of nitric oxide synthase enzymatic activity in peritoneal biopsies. BACKGROUND: Nitric oxide (NO) is synthesized by NO synthase (NOS) isoforms that are expressed in the peritoneum. Thus far, NOS activity in the peritoneum has been assessed by nonspecific methods. We describe the application of a specific method for determination of NOS activity in rat and human peritoneal biopsies. METHODS: The L-citrulline assay is based on the stoechiometric production of NO and L-[3H]-citrulline from L-[3H]-arginine by NOS. The assay is technically difficult when applied on small samples with relatively low levels of NOS activity, which required specific procedures for extraction and samples processing. Reaction parameters ensuring assay linearity in the peritoneum were defined. Peritoneum lysates were also used for immunoblot analysis to identify the NOS isoforms involved. RESULTS: A significant NOS activity is detected in the normal peritoneum because of both Ca2+-dependent and Ca2+-independent NOS. The specificity of NOS activity has been demonstrated by various controls, including the NOS inhibitor L-NMMA. Competition experiments with L-valine and amino acid analyses have reasonably excluded the interference of endogenous arginase and L-arginine, which both might underestimate NOS activity. The procedure is sensitive; it detects a high range of NOS activities as well as the appropriate NOS isoforms in various tissues and conditions, as shown by correlations with immunoblot studies. CONCLUSIONS: We have adapted and characterized the L-citrulline assay to measure specific NOS activities within the peritoneum. The peritoneum lysate assayed for NOS activity can also be used for characterizing NOS isoform expression by immunoblot analysis.
Adult↗