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)     

Silicon metabolism. II. Renal handling in chronic renal failure patients

In 36 patients suffering from chronic renal failure (mean creatinine clearance 26 ml/min), serum silicon levels were significantly increased (mean 0.52 microgram/ml compared with 0.265 microgram/ml in normals; p less than 0.005). Urinary silicon excretion per 24 h was significantly decreased (15.71 mg/24 h compared with 21.4 mg/24 h in normals; p less than 0.001). Fractional excretion of silicon (FESi) was significantly increased in chronic renal failure (p less than 0.001), with overall tubular secretion of silicon in 33% of patients. Urinary excretion of silicon was significantly related to urinary calcium excretion (p less than 0.0001) urinary magnesium excretion (p less than 0.0001) creatinine clearance (p less than 0.05) and sodium excretion (p less than 0.05). It is suggested that urinary silicon is in the form of orthosilicate, principally bound to calcium and magnesium; and that in chronic renal failure the increase in FESi, and the decrease in absorbed Si from the gastrointestinal tract, moderate the increase in plasma silicon levels and prevent excessive entry of silicon into the tissues.     

Renal tubular protein handling in experimental renal disease

Competitive inhibition of renal tubular transport occurs between low- and high-molecular-weight proteins following intravenous infusion, but this relationship is less clear following de novo glomerular or renal tubular injury. The present study evaluated renal lysozyme and albumin handling following renal tubular injury induced by both low- and high-dose mercuric chloride (0.5 and 2.0 mg/kg) and maleic acid (50 and 400 mg/kg), and following glomerular injury induced by puromycin aminonucleoside (5 mg/100 g) or Adriamycin (5 mg/kg). Subtle renal tubular injury induced only mild isolated albuminuria, while severe tubular injury caused dramatic lysozymuria and moderate albuminuria. However, increased filtration of albumin in these models of glomerular injury did not inhibit lysozyme transport.     

Renal replacement in end-stage renal disease patients over 75 years old

BACKGROUND: Over the last decade, the age of dialysis patients has been increasing steadily in several units in Canada. Our main objective was to assess prevalence, co-morbidity and outcome of ESRD patients over 75 years old at the beginning of dialysis treatment in our center. As a group, they were compared to younger dialysis patients treated simultaneously. METHODS: In the last 5 years, all cases beginning dialysis in our institution who were above 75 years of age were reviewed, as well as cases aged between 50 and 60 years who started dialysis during the same period. Between January 1996 and December 2000, among a total of 429 new chronic dialysis patients, 67 ESRD patients over 75 years (15.6%) and 66 patients between 50 and 60 years (15.4%) began dialysis treatment. RESULTS--PRIMARY AND SECONDARY: Diabetes was present in 37% of elderly and in 56% of the younger patients. Younger patients had been referred earlier to our nephrologists than the older ones (42 vs. 27%). Elderly were more frequently treated by hemodialysis than peritoneal dialysis (81 vs. 19%) when compared to their younger counterparts (65 vs. 35%). Long-term catheters for hemodialysis were used more often in elderly patients. No renal transplantation were performed in older patients while 7 younger patients received a renal graft. Survival rates after 1 and 3 years were, respectively, 93 and 74% for patients between 50 and 60 years, whereas it decreased to 80 and 45% for those over 75 years (p = 0.002). More than 50% of patients older than 75 years died within 2 years after starting dialysis; their mean survival was 31 months; patients starting dialysis between 50 and 60 years survived on the average 44 months during the study period. According to the multivariate logistic regression model, risk factors for increased mortality in the older group were: number of hospitalization days during the past 3 months (OR 34.8, 95% CI 8.3-145.7, p < 0.001) and lower weight (OR 16.6, 95% CI 2.0-139.0, p = 0.001). CONCLUSION: We may conclude that, in our hands, life expectancy of patients who began dialysis above 75 years is significantly shorter than for patients for whom dialysis is initiated between age 50 and 60 years, especially if they have a low weight, lose weight and/or require hospitalization.     

Evaluation of renal function in chronic renal disease with special reference to creatinine

Creatinine clearance (Ccr) has been used to evaluate glomerular filtration rate (GFR) in patients with various kinds and grade of renal disease. It is quite useful in terms of simplicity, accuracy and convenience in clinical medicine. However, for the purpose of clinical research, it is not adequate to assess GFR, since a significant quantity of creatinine is secreted in the renal tubule. The secretion rate is rather increased in the endstage chronic renal disease, misleading the true GFR. It also induces an error to calculate the progression rate of a patient with chronic renal failure or to evaluate the effect of the drugs or diet therapy. Therefore, some other indices should be, in future, investigated in order to establish the quantitative evaluation of GFR in patients with chronic renal failure in stead of Ccr or serum creatinine.     

Renal handling of silicon in normals and patients with renal insufficiency.

We have compared the renal handling of silicon in 16 patients with renal insufficiency to 14 normal individuals. Silicon, phosphate and creatinine were measured in plasma and urine samples. The renal insufficiency group showed significant increases in plasma silicon (1.28 +/- 0.19 vs. 0.17 +/- 0.03 mg/liter), creatinine (5.19 +/- 0.85 vs. 0.89 +/- 0.03 mg/dl) and phosphate (1.33 +2- 0.11 vs. 1.07 +/- 0.4 mmol/liter). Fractional phosphate excretion was increased in the renal insufficiency group (0.55 +/- 0.07 vs. 0.14 +/- 0.01). In contrast, the fractional excretion of ultrafiltrable silicon was not significantly different between groups (0.78 +/- 0.07 vs. 0.87 +/- 0.06). It is concluded that renal insufficiency does not alter the tubular handling of silicon and that regulatory control of silicon excretion is unlikely.     

125I-iothalamate and creatinine clearances in patients with chronic renal diseases.

In 196 adult patients with chronic renal disease or primary hypertension, the evaluation of glomerular filtration rate (GFR) by means of creatinine clearance, 'predicted' creatinine clearance and [125I]-iothalamate clearance was performed. Iothalamate clearance was evaluated after subcutaneous injection of the substance . In patients with normal or upper borderline plasma creatinine values, the iothalamate clearance ranged from 44 to 117 ml/min/1.73 m2 and the overestimation of GFR from creatinine clearance was negligible. In patients with mild or advanced renal failure, the overestimation of GFR from creatinine clearance increased up to 18 and 32%, respectively. The clinical usefulness of iothalamate clearance is evident especially in patients with mild renal failure, in whom an accurate evaluation of GFR is often important for a correct dietary and therapeutic approach.     

Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels

Accurate renal function measurements are important for the diagnosis and treatment of kidney disease, proper medication dosing, interpretation of possible uremic symptoms, and decision-making regarding when to initiate renal replacement therapy. Because the use of highly accurate filtration markers to measure renal function has traditionally been limited by cumbersome and costly techniques and the involvement of radioactivity (among other factors), renal function is typically estimated by using specially derived prediction equations. These formulae usually use serum creatinine levels, i.e., a marker of filtration that is insensitive to mild/moderate decreases in GFR. Although attempts have been made to validate certain renal function prediction equations among patients with chronic kidney disease (CKD) with abnormal serum creatinine levels, this is the first study to specifically evaluate the predictive performance of these equations for patients with CKD and serum creatinine levels in the normal range. The results of eight prediction equations for 109 patients with CKD and serum creatinine levels of < or =1.5 mg/dl were compared with standard iohexol GFR values. The most accurate results were obtained with the Cockroft-Gault and Bjornsson equations. The most precise formulae were the Modification of Diet in Renal Disease Study equations, although they were highly biased. Even the most accurate results exhibited levels of error that made them suboptimal for clinical treatment of these patients. These results suggest that measurement of GFR with endogenous or exogenous filtration markers might be the most prudent strategy for the assessment of renal function in the CKD population with normal serum creatinine levels. Further studies are needed to confirm the generalizability of these findings for this patient subgroup.     

Renal replacement therapy in patients with chronic liver disease

As the prevalence of chronic liver disease and chronic kidney disease (CKD) increase, clinicians are likely to be increasingly faced with difficult diagnostic, treatment, and ethical challenges when facing both of these diseases in a single patient. Alterations in creatinine formation and elimination in cirrhotic patients render creatinine-based estimates of glomerular filtration rate and dialysis adequacy less accurate in this population. Furthermore, differentiating signs and symptoms of uremia from hepatic disease may be difficult and clear indications for renal replacement therapy (RRT) in these patients have not been defined. Hemodialysis is associated with a high rate of complications and has not been shown to prolong life in cirrhotic patients with acute renal failure (ARF), but has not been carefully examined in those with CKD. Peritoneal dialysis is, similarly, unhelpful in chronic liver disease complicated by ARF, but has been found to be a viable option in some cirrhotic patients with CKD. Continuous RRT is generally tolerated by patients with decompensated cirrhosis and either acute or chronic renal failure and may act to bridge patients to liver transplantation. Given the poor underlying survival of cirrhotic patients with renal failure, clinicians should carefully consider the utility of RRT in each patient.     

Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old

Introduction

It is known that chronic kidney disease (CKD) and senescence bring about a progressive reduction in glomerular filtration rate (GFR) and that in the former this is usually associated with an increase in the fractional excretion of calcium, phosphorus, magnesium, and uric acid. However, it has not yet been explained how these substances are excreted in the healthy oldest old. Thus, in the present study, we examined the renal handling of these substances in very aged people in comparison with CKD patients with similar GFR levels (stage III??CKD).

Materials and methods

Twenty volunteers were studied; 10 of them were healthy very old (VO) (??75?years old) individuals and 10 were stage III CKD patients. Exclusion criteria were as follows: presence of altered (abnormally high or low) plasma calcium, phosphorus, magnesium and uric acid, as well as previous diagnoses of diabetes mellitus and obstructive uropathy and use of drugs that could alter plasma levels of the studied substances. All volunteers were on a diet with the same content of these elements (3-day dietary register). We measured calcium, phosphorus, magnesium, uric acid, creatinine in serum plasma and morning urine, as well as serum parathyroid hormone level, in each volunteer. From these data, fractional excretion (FE) of these substances was obtained. A statistical analysis was carried out using the Wilcoxon test.

Results

Serum creatinine: 1.8?±?0.4?mg/dl (CKD) versus 0.8?±?0.2?mg/dl (VO), p?=?0.0002; serum calcium: 9.1?±?0.3?mg/dl (CKD) versus 8.7?±?0.4 (VO), p?=?0.022; serum magnesium: 2.3?±?0.2?mg/dl (CKD) versus 2.0?±?0.1 (VO), p?=?0.05; serum phosphorus: 3.9?±?0.5?mg/dl (CKD) versus 3.0?±?0.4?mg/dl (VO), p?=?0.002; serum uric acid: 6.6?±?1.5 (CKD) versus 5.2?±?1.4?mg/dl (VO), p?=?0.04; FE of calcium: 2.5?±?1?% (CKD) versus 0.8?±?0.3?% (VO), p?=?0.04; FE of magnesium: 7.2?±?4.1?% (CKD) versus 2.9?±?0.9?% (VO), p?=?0.02; FE of phosphorus: 25?±?9?% (CKD) versus 9.1?±?5.7(VO), p?=?0.001; FE of uric acid: 10?±?3?% (CKD) versus 8?±?5?% (VO), p?=?0.05.

Conclusion

Serum levels and FE of calcium, phosphorus, magnesium and uric acid were significantly higher in CKD patients compared to healthy very old people with similar GFR, except for serum magnesium and FE of uric acid, which were similar in both groups.     

Perioperative renal functions in patients with chronic renal disease]

Renal function was studied in patients with compensated renal failure and in those with slight renal disorder during and after operations focusing on several aggravating factors. After perioperative episodes of hypovolemia, bleeding and shock, the levels of urine beta 2 microglobulin and FENa were elevated, showing the abnormal renal tubule functions. Elevation of NAG and the decrease of Ccr were observed, showing the organic damage on the renal tubular cell and the influence on GFR. These aggravating factors should be eliminated to prevent the irreversible renal changes.     

Cardiac surgery in patients with chronic renal disease

The combination of chronic renal failure and cardiovascular disease is identified frequently and results in high morbidity and mortality without appropriate medical and surgical therapy. Experience during the last eighteen years has shown that cardiac operations can be undertaken in this high-risk group with acceptable morbidity and mortality and with reasonable expectation of symptomatic improvement. In a six-year period, 17 patients with chronic renal disease underwent cardiac procedures at the Vanderbilt University Affiliated Hospitals. Ten patients were on long-term hemodialysis, and 7 had a functioning renal transplant. Thirteen patients had a coronary artery bypass procedure alone, 1 had a bypass procedure plus aortic valve replacement, 1 had a bypass procedure plus repair of the mitral valve, 1 had a bypass procedure and resection of a left ventricular aneurysm, and 1 had aortic valve and mitral valve replacement for endocarditis. Sixteen patients survived and were discharged. The hospital stay was shorter for patients with a renal transplant than for those on hemodialysis (mean, 11 days versus 22 days, respectively), and perioperative complications were less frequent in the transplant group. There has been 1 late death unrelated to the operative procedure. Fifteen long-term survivors have been followed a mean of 26 months (range 7 to 108 months). All have achieved symptomatic improvement and are in New York Heart Association Functional Class I or II. These results in this high-risk patient group provide a basis for cautious optimism and for a continued aggressive approach in patients with chronic renal disease who require cardiac operation.     

Renal effect of dopexamine hydrochloride in patients with chronic renal dysfunction

Summary Dopexamine hydrochloride, a dopamine analogue, has been reported, both experimentally and clinically, to increase renal blood flow (RBF) and improve renal function in normal kidneys. The availability of computer-enhanced radionuclide scintigraphy, which provides accurate non-invasive measurement of changes in RBF, enabled us to study the renographic effects of dopexamine hydrochloride in patients with chronic renal dysfunction (CRD). Ten patients suffering from CRD and ten normal kidney donors were the study population. Renography was performed, heart rate (HR) and blood pressure (BP) measured, and hematological and biochemical tests carried out before and after intravenous infusion of dopexamine 2 g kg^-1 min^-1 for 60 min. The patient population displayed signficant increases in total cortical and medullary RBF and renographic clearance rate (CR), while in kidney donors the RBF was increased in all kidney regions with no change in CR. HR increased in both groups, while BP showed no significant changes. The hematological and biochemical changes were transient and returned to preinfusion levels after 24 h. It is concluded that dopexamine hydrochloride 2 g kg^-1 min^-1 increases RBF and CR in patients with CRD.This study was carried out in the Urology and Nephrology Center, Mansoura, Egypt, and was partially supported by Fisons plc Pharmaceutical Division, Loughborough, UK.     

Assessing renal function from creatinine measurements in adults with chronic renal failure

Measurement of glomerular filtration rate (GFR) following the injection of one of several suitable marker substances remains the best method to determine the severity of renal insufficiency as well as its rate of progression. However, the expense of these procedures continues to restrict their use. A second alternative is the determination of creatinine clearance (CCr) after oral administration of cimetidine. This drug blocks tubular secretion of creatinine almost completely, and CCr measured under these conditions is reported to be nearly identical to GFR in mild or severe renal failure. The optimal dose and timing of cimetidine for this purpose is still uncertain, but a single 1,200-mg dose 2 hours before beginning urine collection is probably suitable. A third alternative is simply the measurement of serum or plasma creatinine (PCr) concentration. However, it is well established that substantial reductions in renal function may occur before PCr becomes abnormal. GFR in adults with chronic renal failure can be approximately estimated from PCr, provided it is greater than 2 mg/dL, with the aid of additional demographic and biochemical variables. Gender, height, weight, age, and race should be taken into account. Further study is needed to derive the best formula for predicting GFR from PCr and other variables. Finally, CCr (without cimetidine) is still in use. This is unfortunate because it has been established that rather than improving on the estimation of GFR from PCr, CCr (determined from urinary creatinine measurements as well as PCr) is a less reliable guide to GFR than PCr alone. The CCr/GFR ratio is almost always greater than unity and increases with decreasing GFR to a maximum of approximately 1.7 at a GFR of approximately 20 mL/min. Furthermore, the variability of CCr is greater than that of PCr. Measurement of CCr (without cimetidine) is an anachronism and should be abandoned.     

Comparisons of cystatin C with creatinine for evaluation of renal function in chronic kidney disease

Background  

Because of the limitations of creatinine (Cr) as a marker for the glomerular filtration rate (GFR), cystatin C (CysC) has been proposed as an alternative substance. The aim here was to clarify the characteristics of CysC compared with Cr.     

Calcium metabolism in patients with chronic non-dialytic renal disease

Calcium metabolism was evaluated in 81 patients with chronic non-dialytic renal disease. Bone mineral content measured by photon absorptiometry was significantly lower than in normals, and serum alkaline phosphatase levels higher than in normals. However, the differences were small indicating that the calcium-metabolic disturbance was moderate. None of the patients suffered from overt osteomalacia. The mean serum level of 25-hydroxy-cholecalciferol (25-OH-D₃) was slightly, but significantly higher than in normals studied at the same time of the year, but some patients and subnormal 25-OH-D₃ levels. One such patient was given a daily dose of 1200 U of vitamin D₃ by mouth for 3 weeks. Hereafter, the serum 25-OH-D₃ concentration rose progressively to high normal values. These two observations would suggest that the hepatic 25-hydroxylation in such patients is unimpaired. The results are in accordance with the existence of a subclinical vitamin D deficiency in patients with non-dialytic renal disease, due to an impaired production of 1,25-(OH)₂D₃. It is an open question whether such patients should be given (prophylactic) treatment with 1α-hydroxycholecalciferol.