Urinary citrate excretion in normal persons and patients with idiopathic calcium urolithiasis

The 24-hour urinary excretion of citrate was measured in 83 normal persons and in 132 consecutive patients with idiopathic calcium urolithiasis, uninfected urine, and normal renal function. The urinary excretion of citrate in normal men was not significantly different from that in normal women (P greater than 0.05). There was a significant (P less than 0.001) increase of urinary citrate excretion with increasing age in normal persons. No increase of urinary citrate excretion with age was demonstrated in stone formers. There was no statistically significant difference between active and inactive stone formers in regard to regression of the citrate/calcium ratio or the citrate/uric acid ratio, and there was no difference in these ratios between men and women considered separately or in subgroups by hypercalciuria or hyperuricuria or by individual age. Hypocitraturia was found in 29.2% of patients with idiopathic calcium urolithiasis. No relationship could be demonstrated between the 24-hour urinary excretion of citrate and severity of stone disease before presentation at our clinic or the frequency of stone growth or new stone formation at follow-up. Twenty-two of 35 patients with hypocitraturia had multiple urinary citrate measurements. In 15 of these 22 patients, at least one normal urinary citrate measurement was obtained. Further prospective study is required to establish the value of urinary citrate determinations in patients consuming an uncontrolled diet in an outpatient setting.     

Urinary excretion of complement C3d in patients with renal diseases

INTRODUCTION: Complement-mediated tubular injury may play an important role in the progression of renal diseases. C3d is a presumed marker of complement activation. Its precursor C3dg has been detected in the urine of patients with membranous nephropathy. However, little is known of the renal handling of C3d or its excretion in other renal diseases. METHODS: We measured the urinary excretion of albumin, IgG, beta2-microglobulin (beta2m), and of complement C3d in patients with tubulo-interstitial nephritis (TIN; n= 8), in patients with membranous nephropathy (n = 35) and in patients with nonmembranous glomerular diseases (23 nonproliferative and 21 proliferative). Fractional excretions (FE) were calculated using creatinine clearance as marker of GFR. RESULTS: C3d was not measurable in the urine of the healthy controls, but was detectable in seven out of eight of the TIN patients (median excretion 0.11 mU min-1, range 0.006-2.4 mU min-1). In these patients the urinary excretion of beta2m was clearly elevated (median 26.6 micro g min-1, range 1.0-103 micro g min-1). The FE of C3d correlated with the FE of beta2microglobulin (r = 0.83, P = 0.01), and their ratio amounted to 0.03 (range 0.003-0.06), a value in agreement with the expected sieving coefficient. Urine C3d was detectable in all but three of the patients with glomerular diseases (median excretion 0.36 mU min-1, range 0.004-7.9 mU min-1); C3d-excretion did not differ between the three subgroups of patients with glomerular diseases. FEC3d correlated with FEIgG (r = 0.88, P < 0.01). The ratio FEC3d/FEbeta2m was 0.78 (range 0.04-9.99). Selected patients with membranous nephropathy were re-analyzed after (partial) remission of proteinuria. Reduction of proteinuria resulted in a decrease of C3d excretion. CONCLUSION: Urinary excretion of C3d is elevated in patients with TIN, most likely as a mere consequence of decreased tubular reabsorption. In patients with glomerular diseases urinary excretion of C3d is increased and related to proteinuria, independent of the underlying glomerular disease. In these patients there is evidence of increased local formation of C3d.     

Urinary response to oral potassium citrate therapy for urolithiasis in a private practice setting

Oral potassium citrate therapy was recently approved for treatment of urolithiasis based on results of experiments in a university research setting. However, no supporting studies from private practice have been published. The present study was undertaken to assess the response to one week of oral potassium citrate therapy (60 mEq/day), with respect to urinary risk factors for kidney stones, in a private practice setting. A significant rise in urinary pH, citrate, and potassium excretion, accompanying a significant fall in calcium excretion, were observed. Urinary saturation of calcium oxalate was significantly reduced, as some risk factors in urolithiasis were corrected with oral potassium citrate therapy. The response to therapy in private practice was comparable to that observed in a university research setting.     

Insulin resistance and low urinary citrate excretion in calcium stone formers.

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p<0.05), whereas no difference was detected as far as urinary oxalate, calcium, uric acid, phosphate, and urine pH and urine volume output were concerned. HOMA-IR values were positively related to uric acid serum levels (r=0.31, p<0.05) and negatively to urinary citrate excretion (r=-0.26, p<0.05). Hypocitraturic patients showed higher levels of HOMA-IR than normocitraturic ones (3.03+/-0.92 vs. 2.25+/-1.19, p<0.05). This study shows that a higher level of insulin resistance is associated with lower urinary citrate excretion, and that hypocitraturic patients show a greater insulin resistance than normocitraturic calcium stone formers. This may be related to changes in citrate, Na(+)-K(+) and H(+) renal tubule transports, which have been described in insulin resistance. In conclusion, insulin resistance may contribute to an increased risk of calcium stone formation by lowering urinary citrate excretion. This finding suggests the need for a careful metabolic assessment in patients known to form calcium stones in order to ensure stone recurrence prevention and cardiovascular protection.     

Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion.

1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion.     

Urinary excretion of angiotensin-converting enzyme in NIDDM patients with nephropathy

Twenty-four-hour urinary excretion of angiotensin-converting enzyme (ACE) was investigated in relation to that of albumin and beta 2-microglobulin (beta 2M) in 25 non-insulin-dependent diabetes mellitus (NIDDM) patients without nephropathy, 13 NIDDM patients with incipient nephropathy, 18 NIDDM patients with overt nephropathy, and 14 nondiabetic subjects. NIDDM patients without nephropathy and nondiabetic subjects were similar in albumin, beta 2M, and ACE excretion. NIDDM patients with incipient nephropathy had elevated albumin excretion (P less than .01) and similar beta 2M and ACE excretion compared with nondiabetic subjects. On the other hand, NIDDM patients with overt nephropathy had elevated albumin, beta 2M, and ACE excretion compared with nondiabetic subjects (P less than .01). In all NIDDM patients studied, a positive correlation was found between ACE excretion and albumin excretion (r = 0.76, P less than .001) or beta 2M excretion (r = 0.52, P less than .01). These data suggest that elevated ACE excretion in NIDDM patients with overt nephropathy may be reflective of renal tubular damage.     

Urinary kallikrein excretion during potassium chloride infusion in potassium-adapted rats: effect of amiloride

1. Urinary kallikrein excretion in the anaesthetized rat was measured during intravenous KCl infusion in control and in K+-adapted rats. 2. The infusion of 0.1 mol/l KCl at 3.0 ml/h for 60 min in control rats resulted in a significant increase in urinary kallikrein excretion, associated with diuresis, natriuresis and kaliuresis. 3. When rats were offered 0.1 mol/l KCl to drink ad libitum for 14 days (K+-adaptation), the basal excretion of kallikrein was higher than in the control rats. In K+-adapted rats, intravenous infusion of 0.1 mol/l KCl resulted in significantly greater increase in urinary kallikrein excretion than in the control rats. 4. The Na+-channel blocker, amiloride (8.5 mg/kg body weight), significantly increased urinary kallikrein excretion immediately after injection in control and K+-adapted rats. However, in the subsequent 60 min, kallikrein excretion decreased markedly to values lower than those before injection of amiloride. 5. When amiloride was superimposed on a continuous 0.1 mol/l KCl infusion in K+-adapted rats, there was an immediate increase in kallikrein excretion. In the subsequent 20 min, kallikrein excretion decreased only to increase again in the next 40 min of KCl infusion. 6. Since amiloride injection reduces urinary kallikrein excretion in control and K+-adapted rats, the results suggest that urinary kallikrein excretion in the rat is through a mechanism(s) affected by amiloride. The high urinary kallikrein excretion and the greater response to KCl infusion in K+-adapted rats suggest that the K+-transport mechanism is more important than the mechanism affected by amiloride.     

Heparin versus citrate for anticoagulation in critically ill patients treated with continuous renal replacement therapy

Background: Continuous renal replacement therapy (CRRT) is commonly used in the care of critically ill patients ( Gabutti et al., 2002 ). Critical illness increases the likelihood to both coagulation and bleeding, making anticoagulation for CRRT problematic. Aims: This mini‐review aims to examine the evidence that compares the use of systemic heparin and regional citrate as forms of anticoagulation for CRRT in critically ill patients. The primary outcome of interest was haemofilter circuit survival, and the secondary outcome was reduced risk of bleeding. Search strategy: A systematic literature search was undertaken to identify all studies comparing these drugs. The Cochrane Library , Medline and Embase databases were searched. Eighty‐nine articles were found. Included studies were randomized controlled trials (RCTs), which used a target population of critically ill adults. Studies were excluded if they had not been written in English and if they were not available through King’s College London. After applying the inclusion and exclusion criteria, three RCTs comparing the use of systemic heparin and regional citrate were included in the review. Results: Two studies showed significant differences in circuit survival time, with citrate prolonging survival time. All studies showed an increased risk of bleeding in the heparin group, resulting in a higher rate of transfusion while heparin was being used. Conclusions: The studies examined lacked reference to the power of the studies and strength in the presentation of the results. Because of the lack of reliability in the studies, it would be suggested that further research is needed on this topic in order to produce rigorous high‐quality reviews with limited bias. The use of citrate, as with all treatments in clinical practice, should be used with caution and assessed on an individual patient basis. Reviewing this evidence helps to gain an insight into different treatment options available, identifying some of the risks and benefits.     

The antihypertensive and renal activities of potassium canrenoate are associated with increased renal prostaglandin excretion

1. In a double-blind, randomized, cross-over study the effects of potassium canrenoate administration (100 mg twice daily for 10 days orally) on renal prostaglandin synthesis (prostaglandin E2 and prostaglandin F2 alpha) were evaluated in 10 normotensive females and in 10 females with essential hypertension. 2. When compared with normotensive subjects, hypertensive patients in baseline conditions showed a reduced excretion of urinary prostaglandin E2 associated with an excessive prostaglandin F2 alpha production. 3. Potassium canrenoate significantly reduced mean blood pressure in hypertensive patients [from 118.9 +/- 8.7 mmHg (1.62 +/- 0.12 kPa) to a peak minimum value of 104.7 +/- 9.8 mmHg (1.42 +/- 0.13 kPa) on the seventh day of treatment; P less than 0.01 for the whole period] but not in control subjects [from 88 +/- 9.4 mmHg (1.20 +/- 0.13 kPa) to 84.3 +/- 8.3 mmHg (1.15 +/- 0.11 kPa) on the eighth day, NS] even though potassium canrenoate significantly increased sodium excretion in both groups. Renal prostaglandin excretion was affected differently in the two groups: in control subjects excretion of both prostaglandin E2 and prostaglandin F2 alpha was increased after drug administration, whereas in hypertensive patients only prostaglandin E2 excretion was enhanced.     

枸橼酸局部抗凝在肝功能不全患者连续性肾脏替代治疗中的安全性评价

目的 评估枸橼酸局部抗凝(RCA)在肝功能不全患者连续性肾脏替代治疗(CRRT)中的安全性。方法 回顾性分析东部战区总医院(秦淮医疗区)重症医学科收治的56例行CRRT治疗的患者资料。患者分为肝功能正常组20例、肝功能轻中度异常组20例以及肝功能重度异常组16例,观察3组患者的滤器使用时间,监测各组的肝肾功能、凝血功能、酸碱及电解质、钙比值等相关指标。结果 3组间患者滤器使用时间比较,差异无统计学意义(P>0.05)。治疗后,肝功能轻中度异常组及肝功能重度异常组患者肌酐(Cr)较治疗前均降低,差异有统计学意义(P <0.05);3组间Na^+、总钙较治疗前的变化幅度比较,差异有统计学意义(P <0.05);余下指标比较,差异均无统计学意义(P均> 0.05)。肝功能轻中度异常组及肝功能重度异常组患者均出现少量枸橼酸盐蓄积的情况。结论 肝功能异常组(中度和重度)相比肝功能正常组滤器使用时间相当,未对酸碱及电解质等内环境指标产生严重影响,脏器功能、凝血状态治疗前后无差别。仅少数患者存在一定程度的枸橼酸盐蓄积,但未出现严重并发症,考虑安全性尚可。     

枸橼酸钠抗凝连续性肾脏替代治疗救治尿毒症脑出血患者的优势

目的 探讨枸橼酸钠抗凝连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)在救治尿毒症脑出血患者中的优势.方法 2012年1月至2020年6月尿毒症脑出血患者44例,根据抗凝方式分为枸橼酸钠抗凝CRRT组(n=17)和无肝素CRRT组(n=27),比较两组生存率及各指...     

Urinary lysosomal glycosidases after renal allotransplantation: correlation of enzyme excretion with allograft rejection and ischemia

Urinary β-galactosidase, β-glucuronidase and N-acetyl-β-glucosaminidase were measured in patients with renal allotransplants and compared with normal controls. Increased excretion of all three enzymes was noted in the transplant patients resulting possibly from mild chronic rejection.A second part of the investigation correlated renal function with daily N-acetyl-β-glucosaminidase excretion by the patients. In acute rejection, enzyme levels rose sharply from a baseline then decreased following successful treatment. With cadaveric grafts and initially good urinary flow, N-acetyl-β-glucosaminidase levels were high and decreased as creatinine clearance improved; however, with initial oliguria, levels were low and rose as diuresis began then decreased to a baseline. This was attributed to a washing out of enzyme released during the unavoidable ischemic period involved in handling cadaver kidneys.Because it reflects physiological changes in the kidney, daily monitoring of urinary N-acetyl-β-glucosaminidase should be helpful in the diagnosis of renal damage caused by rejection and ischemia.