Different Degrees Of Renal Insufficiency Research Articles

Clinical and Pathological Characteristics of Related-Renal Damage in Patients with POEMS Syndrome

To investigated the clinical and pathological characteristics of related-renal damage in patients with POEMS syndrome. Five patients diagnosed as POEMS syndrome in our hospital were selected. Their clinical manifestation, pathological characteristics of kidney and laboratory examination were analyzed retrospectively. Among the 5 patients, three males and two females with a median age of 50 years old. The mean interval before diagnosis was 13.0±7.2 months. All the patients showed neuropathy, endocrinopathy, monoclonal plasma cell-proliferative disorder, skin changes and extravascular volume overload, in which 4 patients showed organomegaly. Proteinuria was found in 5 patients, and microhematuria was found in 4 patients. Moreover, 4 patients showed an elevated blood urea, while 2 patients showed creatinine elevation. 1 patient at chronic kidney disease (CKD)-G1 stage, 2 patients at CKD-G2 stage, and 1 patient at CKD-G3b stage, moreover, 1 patient at CKD-G5 stage. Endothelial injury and mesangial lesion were the main characteristics of renal pathology. 3 patients were pathologically diagnosed as thrombotic microangiopathy kidney damage, while 2 patients as light chain amyloidosis. POEMS syndrome is a multi-systemic disease with complex clinical manifestations. 5 patients had different degrees of renal insufficiency. Endothelial injury and mesangial lesion are the main features of renal pathology.

Characteristics of clinical drugs for elderly chronic heart failure complicated with different degrees of renal insufficiency.

Objective:To investigate the characteristics of clinical therapeutic drugs in elderly chronic heart failure (CHF) patients complicated with different degrees of renal insufficiency.Methods:The elderly patients who were hospitalized from October 2010 to October 2015 in our hospital due to CHF for the first time were selected by means of retrospective case collection. The glomerular filtration rate was estimated by using the Modification of Diet in Renal Disease (MDRD) Study equation. The patients were divided into a group with normal renal function, a group with slight decrease in renal function, and a group with moderate and severe decrease in renal function. Statistical analysis was made to compare the characteristics of clinical drugs for the three groups.Results:Compared with the normal renal function group and the slight decrease group, ACEIs and β-blockers were less used in the moderate and severe decrease group, but diuretics and spironolactone were more used (P<0.05). Compared with the normal renal function group, the use rate of ACEIs was low whereas that of diuretics was high (P<0.05).Conclusion:ACEIs and β-blockers were barely employed to treat elderly CHF patients complicated with renal insufficiency, but diuretics and spironolactone were frequently utilized.

Evaluation of the Single-dose Pharmacokinetics of Bilastine in Subjects with Various Degrees of Renal Insufficiency

BackgroundBilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries.ObjectiveThis study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin.MethodsThe study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18–80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m2]; (2) mild renal insufficiency (GFR 50–80 mL/min/1.73 m2); (3) moderate renal insufficiency (GFR 30–50 mL/min/1.73 m2); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m2). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics.ResultsThere was a clear trend of increasing area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) through the groups 1–4. The mean AUC from time zero to infinity (AUC∞) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among groups in median time to reach Cmax (tmax) or in the mean terminal disposition rate constants for bilastine were found. Renal and plasma clearance paralleled GFR. In all groups of renally impaired subjects the corresponding 90 % confidence interval of both AUC∞ and AUC from time zero to time of last measurable plasma concentration (AUClast) were not within the 0.8–1.25 interval, indicating that bioequivalence between groups could not be demonstrated. The majority of bilastine was excreted within the first 12 h, and elimination was essentially complete by 72 h.ConclusionAn oral dose of bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase in exposure. The oral plasma clearance to renal clearance ratio [(CLP/F)/CLR] was approximately equal in the different groups, suggesting that renal excretion was the main elimination route for bilastine, and no alternative elimination routes were used even in severe renal insufficiency. Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

Treatment with calcimimetics in kidney transplantation

Graft and patient survival in renal transplantation has increased with better immune suppression treatment, leading to the appearance of new complications such as posttransplant bone disease. After renal transplantation and the recovery of renal function, mineral metabolism disorders secondary to renal failure could be expected to normalize. However, both immediately after transplantation and later, and even with good renal graft function, we see bone disorders associated to renal osteodystrophy, a high incidence of osteopenia, persistent hyperparathyroidism, hypercalcemia, hypophosphoremia, and less commonly, aseptic bone necrosis. The causes potentially responsible for these disorders have basically been identified as different degrees of renal insufficiency in the graft, persistent posttransplant secondary hyperparathyroidism, and negative impact of immunosuppression treatment, particularly corticosteroids. The most important factor in the evolution of metabolic and bone disorders after renal transplantation, however, is pretransplant bone status. Special attention should be paid to other osteoarticular complications such as loss of bone mass and fractures, leading to significant morbidity. In the therapeutic approach to these patients, as well as encouraging physical exercise and advice about diet or other habits, the use of drugs such as calcium and vitamin D supplements, bisphosphonates, and more recently, calcimimetics have made significant improvements in the prevention and treatment of bone-mineral metabolism. It has been shown that calcimimetic agents can control the parathyroid hormone, reduce episodes of hypercalcemia, and improve hypophosphatemia. Their properties have to be assessed in broader studies to establish the basis for their widespread use among renal transplant recipients.

Abstract 5579: Myocardial Infarction, Clinical Characteristics and Prognosis across Five Renal Function Stages - Data from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA)

Assess clinical characteristics, presentation and prognosis following a myocardial infarction (MI) at different degrees of renal insufficiency. Nearly all consecutive patients in Sweden with MI treated at a coronary care unit between 2003–2006 and who had either known creatinine or received dialysis (n=58496, 90.4% of entire cohort) were followed. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease formula and staged according to the National Kidney Foundation definition. Cox regression analysis adjusting for 30 variables including baseline characteristics, symptoms on admission, ECG-pattern, reperfusion therapy and discharge medication was used to assess mortality with eGFR both as a continuous and categorical variable. Patients with declining renal function differed by being older and having more comorbidites such as diabetes, hypertension and prior MI. Fewer patients with kidney failure presented with chest pain compared to those with normal eGFR≥90 ml/min/m2 (66.2% versus 90.2%). They had a non-ST-elevation MI more often (67.7% versus 55.7%) and clinical heart failure (45.0% versus 10.7%) on admission. Overall, at 30 days and 1 year, 8.5% and 16.4% patients had died. After adjustment, 30-day and 1-year mortality was significantly higher in those with more advanced renal insufficiency (Table ). For every 10 ml decrease in eGFR 30-day mortality increased by 3.1% (95% CI 1.00 –1.06, p=0.025), whereas 1-year mortality increased exponentially. Patients with renal insufficiency differ in presentation pattern for a MI. Although 30-day mortality increases linearly with worsening renal function, 1-year mortality differs by increasing exponentially, leading to extremely high mortality rates in those with severe renal insufficiency. Research into disease mechanisms and advances in therapies are needed to enhance outcome. Mortality following a MI across renal function groups

ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy.

In this post hoc, secondary analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, an angiotensin-converting enzyme (ACE) inhibition risk/benefit profile was assessed in 322 patients with nondiabetic, proteinuric chronic nephropathies and different degrees of renal insufficiency. The rate of GFR decline (Delta GFR) and the incidence of end-stage renal disease (ESRD) during ramipril or non-ACE inhibitor treatment were compared within three tertiles of basal GFR. Delta GFR was comparable in the three tertiles, whereas the incidence of ESRD was higher in the lowest tertile than in the middle and highest tertiles. Ramipril decreased Delta GFR by 22%, 22%, and 35% and the incidence of ESRD by 33% (P < 0.05), 37%, and 100% (P < 0.01) in the lowest, middle, and highest tertiles, respectively. Delta GFR reduction was predicted by basal systolic (P < 0.0001), diastolic (P = 0.02), and mean (P < 0.001) BP and proteinuria (P < 0.0001) but not by basal GFR (P = 0.12). ESRD risk reduction was predicted by basal proteinuria (P < 0.01) and GFR (P < 0.0001) and was strongly dependent on treatment duration (P < 0.0001). Adverse events were comparable among the three tertiles and within each tertile in the two treatment groups. Thus, disease progression and response to ACE inhibition do not depend on severity of renal insufficiency. The risk of ESRD and the absolute number of events saved by ACE inhibition is highest in patients with the lowest GFR. However, renoprotection is maximized when ACE inhibition is started earlier and when long-lasting treatment may result in GFR stabilization and definitive prevention of ESRD.

Plasma clearance of iodine contrast media as a measure of glomerular filtration rate in critically ill patients.

The selection of the optimal method for assessing renal function relies on the accuracy of the technique. Plasma clearance of nonradioactive iodine contrast media (i.e., iohexol or iopromide) has been suggested as a reliable alternative to the renal clearance of inulin for estimating glomerular filtration rate (GFR). The accuracy of this method when used with critically ill patients displaying different levels of renal function in an intensive care unit (ICU) has not, until now, been examined. The accuracy of double- and multiple-point iohexol or iopromide plasma clearances was compared with that of already established techniques for measuring GFR (creatinine clearance, formula clearance by Cockcroft and Gault) and with that of inulin clearance, which is regarded as the gold standard for the measurement of GFR. Values were obtained from 31 ICU patients who exhibited a wide range of renal function (serum creatinine: 0.6-6.7 mg/dL). Inulin clearance was performed using the constant-infusion technique. Creatinine clearance was determined from 24-hr urine samples. The clearance formula was calculated according to Cockcroft and Gault's formula. Iohexol or iopromide were applied as a single intravenous dose, and blood samples were taken up to 6 hrs after the injection. Iodine concentrations were determined by radiographic fluorescence. Plasma clearance of iohexol/iopromide measured after the single injection of contrast media and that of the conventional inulin clearance was almost identical (y = 0.971x + 7.65, r2 =.96; n = 31). Two-point clearance of iohexol/iopromide (double sampling technique) was as reliable as the three-point clearance (three-slope-intercept method, y = 0.995x + 0.62, r2 =.999; n = 18). With respect to inulin clearance, GFR measurements determined by creatinine clearance or according to the formula given by Cockcroft and Gault revealed errors that increased proportionally (y = 1.03x, r2 =.88; n = 27; and y = 0.93x, r2 =.62; n = 31, respectively). It could also be shown that the accuracy of GFR measurements involving plasma clearance of iohexol was not greatly affected by the degree of renal insufficiency or the route by which contrast media were applied. These findings indicate that the determination of plasma clearance of iohexol/iopromide is a simple, rapid, and accurate method that can indeed be used for estimating GFR in ICU patients with normal renal function or even different degrees of renal insufficiency.

Pharmacokinetics of clodronate in renal failure.

The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection. The renal clearance (CLR) of clodronate was highly dependent on renal function and declined successively with declining glomerular filtration rate (GFR). Plasma clearance (CLP) declined, too, but to a lesser degree than CLR. The impairment of renal function resulted in decreased cumulative urinary elimination of clodronate and increased total areas under the serum concentration-time curve (AUC0-infinity). Hence, as the renal elimination of clodronate diminishes with decreasing GFR, there is a related retention of the substance. As a result of the present study, the following dosages are recommended: creatinine clearance (CLCr) from 50 to 80 ml/minute, 75-100% of normal dose; CLCr 12-50 ml/minute, 50-75% of normal dose; and ClCr < 12 ml/minute, 50% of normal dose. The results must be interpreted with caution in patients with malignancy and severe skeletal disease, in whom the nonrenal clearance may vary markedly.

Pharmacology of r-hirudin in renal impairment

The pharmacokinetic properties of r-hirudin were studied in nine patients suffering from different degrees of renal insufficiency. To this end, r-hirudin was administered intravenously at dosages of 0.1 mg/kg. The elimination half-life t 1 2β was determined in blood plasma and the cumulative r-hirudin excretion in urine was measured over 48 h. In healthy volunteers t 1 2β was 0.9 ± 0.2 h; the cumulative r-hirudin excretion in urine after 48 h amounted to 38 ± 10 % of the dose administered, most of this quantity was excreted during the first hours. In seven patients with chronic renal failure, t 1 2β was 15 to 41 h; in three of these patients cumulative urinary r-hirudin excretion was increased to 70 – 80 %, in four patients cumulative r-hirudin excretion in urine within 48 h amounted to 39 ± 8 %, but was delayed in time. In 2 bilaterally nephrectomized patients, t 1 2β was 168 and 316 h, resp. The renal clearance of hirudin was significantly and linearly correlated with the creatinine clearance (r=0.872). In all patients aPTT and bleeding time were only moderately prolonged. Because of the modified pharmacokinetic behaviour the administration of hirudin in patients with impaired renal function requires individually adjusted dosages or prolonged administration intervals.

Renal Handling of Citrate in Chronic Renal Insufficiency

Citrate is a relevant component of the inhibitory potential of the urine environment. Its excretion and renal handling have been widely studied in subjects with normal renal function, but little is known about changes induced by chronic renal insufficiency. We have investigated renal handling of citrate in 50 patients with different degrees of renal insufficiency as compared to 30 healthy subjects with normal renal function. Among patients 34 were defined as having mild renal insufficiency based on a GFR of 80 through 40 ml/min/1.73 m2 BSA, while 16 had moderate-to-severe renal failure, defined by a GFR ranging from 40 to 20 ml/min/1.73 m2 BSA. Serum citrate increased in mild renal insufficiency, while it tended to be restored to normal values at more advanced renal failure. There was a stepwise decrease in the filtered load of citrate as GFR decreased, while its renal clearance was significantly reduced only at higher degrees of renal failure. This behavior was due to an increase in the fractional excretion of citrate which was inversely related to the decrease in GFR (p = 0.015). These data suggest that serum citrate levels and excretion are governed by renal mechanisms at mild degrees of renal insufficiency; in these conditions citrate is shown to behave conformly to other poorly reabsorbable anions such as sulfate. At more advanced renal failure the ensuing metabolic acidosis plays a crucial role as a regulatory factor of both serum concentration and renal handling of citrate, by increasing cellular uptake and metabolism as well as tubular reabsorption of this anion.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of imipenem (thienamycin-formamidine) and the renal dehydropeptidase inhibitor cilastatin sodium in normal subjects and patients with renal failure.

The antibiotic imipenum (thienamycin-formamidine) is partially hydrolyzed during excretion by a renal brush border dehydropeptidase. The co-administration of imipenum with the renal dehydropeptidase inhibitor cilastatin results in an increase of the urinary recovery of the antibiotic, both in animals and humans. To study the pharmacokinetics of imipenem and cilastatin, subjects with normal renal function and patients with different degrees of renal insufficiency received intravenously 250 mg imipenum alone and 250 mg imipenem with 250 mg cilastatin. The mean plasma half-life of imipenem varied from 52 min in subjects with normal renal function to 173 min in subjects with end-stage renal failure studied while off-dialysis. The plasma half-life of imipenem was not affected by the co-administration of cilastatin. The mean plasma half-life of cilastatin varied from 54 min in normals to 798 min in patients with end-stage renal failure. The co-administration of cilastatin resulted in an increase of the urinary concentration and in the urinary recovery of imipenem, the effect being more pronounced in the subjects with normal or only mildly impaired renal function. The plasma clearance of imipenem was decreased when cilastatin was co-administered, possibly due to inhibition of tubular secretion of imipenem. Elimination studies performed during haemodialysis indicated efficient removal of both imipenem and cilastatin during a 4 h session. In view of the important increase in half-life of cilastatin as a function of increasing renal failure, a dosage reduction is proposed in patients with severe renal failure. It is recommended that the maximum dose of imipenem/cilastatin would be limited to either 1000/1000 mg twice daily or 500/500 mg four times daily in patients with a creatinine clearance of less than 15 ml/min. Also, a supplementary dose of imipenem and cilastatin after dialysis is recommended.

Blood and urinary concentrations of fosfomycin as a function of the renal function value.

The following parameters were considered in studying 43 subjects under treatment for urinary infections with different degrees of renal insufficiency: the maximum blood concentrations, the plasmatic half-life, and the urinary concentrations of fosfomycin as a function of the plasma creatinine of the subject treated. The curve of the average maximum blood concentrations show a parabola-like increase, the plasmatic half-life followed the same tendency, while the curve of the average urinary concentrations presented an exponential decrease. The urinary concentrations were, nevertheless, always higher than 100 mug/ml regardless of the degree of renal insufficiency and even in the subjects who had a very high plasma creatinine. Given its absence of renal and systemic toxicity, the daily dosage of fosfomycin could remain unchanged regardless of the degree of insufficiency.