Effect of renal function on cytokine secretion of monocytes and lymphocytes

The effect of renal function on cytokine secretion capacityof mononuclear cells was analysed in patients who had not beensubjected to any form of renal replacement therapy. The aimof the study was especially to determine whether there is adefect of monocyte function. The patients were divided intothree groups of 12 on the basis of renal function: group I,serum creatinine 1.5–3 mg/dl; group II, 3–6 mg/dl;and group III, >6 mg/dl. Serving as controls were 36 age-and sex-matched healthy volunteers. IL-1ß, IL-6, TNF-,IL-2 and IF- concentrations were measured in the supernatantsof stimulated and unstimulated cells isolated from the blood.Renal function was not found to have any effect on the secretioncapacity of IL-2 and IF-. However, the secretion capacity ofIL-1ß of lipopolysaccharide (LPS)-stimulated monocyteswas reduced in patients of group III to 214±290 pg/ml,compared with 501±327 pg/ml in controls (P=0.047). Theeffect was even more accentuated for IL-6 (group III: 5422±5116pg/ml; controls: 16319±12474 pg/ml; P=0.019). Spontaneoussecretion levels did not change for any of the cytokines, andLPS-stimulated TNF- secretion was also normal. Highly purifiedblood monocytes/macrophages were stained for CD14, HLA-DR, CD11c,and CD4. Neither the percentage of positive cells nor the fluorescenceintensity, as measured by FACS, was influenced by renal function,and no correlation could be established between function andphenotype. The data show clearly a reduced secretion capacityof IL-1ß and IL-6 in patients with severely impairedrenal function.     

人工气道建立后气道钠负荷对呼吸道分泌物清除的影响

目的探讨人工气道建立后气道不同钠负荷对呼吸道分泌物清除的影响。方法对45例建立人工气道的患者采用自身对照法应用0.9%氯化钠或2.0%氯化钠溶液进行雾化吸入。比较2种浓度雾化吸入后示踪物首次出现时间和雾化吸入前后BP、HR及SpO2的变化。结果2.0%氯化钠溶液雾化吸入后示踪物出现时间为(1.05±0.51)h,0.9%氯化钠溶液雾化吸入后为(1.22±0.44)h,前者示踪物出现时间显著早于后者(P<0.01);两者BP、HR及SpO2比较,差异无显著性意义(均P>0.05)。结论2.0%氯化钠溶液雾化吸入安全,有利于呼吸道纤毛转运,使排痰速度加快。     

Renal venous erythropoietin concentrations in hypertensive patients with unilateral renal disease.

In 24 hypertensive patients with unilateral renal disease, the erythropoietin (Epo) concentration ratio in the renal veins was compared with the renin ratio. Seven patients showed moderately elevated peripheral Epo values. Epo and plasma renin activity were significantly positively correlated both in peripheral and renal veins. This suggests that the reduction of renal blood flow was a common, but not unique, stimulating factor of Epo and renin secretion. Epo ratio appeared insensitive since it was greater than 1.5 in only 30% of patients with a renin ratio > 2. Our results indicate that the Epo concentration ratio in renal veins cannot be proposed as a substitute for the currently used renin ratio.     

Effects of Sodium Valproate on Renal Functions in Rats

In recent years, it has been reported that sodium valproate occasionally can cause renal tubular impairment. This study was designed to demonstrate the renal tubular and glomerular functions in rats given sodium valproate as monotherapy, as well as to determine any reversibility of dysfunctions. Female rats were randomly allocated to three groups: group 1 received sodium valproate 500 mg/kg/d intraperitoneal for six weeks; after the same injection period, group 2 was housed for another six weeks, after which laboratory investigations were completed; and group 3 served as a control group made up of 20 healthy rats living in same condition without any treatment. Serum ALT, total protein, uric acid, ALP, phosphorus, sodium levels, and urine Ca/cr ratio were significantly different between groups 1 and 3 (p?<?0.025), but this difference was not seen between groups 2 and 3. On the other hand, other parameters such as TRP, Ccr, NAG, and MDA were not significantly different among the three groups (?p?>?0.025) These results suggest that SV does not have a significant dose- or time-related side effect on renal functions. Minor biochemical dysfunctions related to long-term sodium valproate therapy is reversible, and the minimal renal fibrosis that showed histopathologically is not clinically important. The renal tissues of rats are known to show similar metabolic and histological patterns with human renal tissues. No renal dysfunction was expected in humans because there were no clinically statistically significant renal side effects in this study.     

Creatinine Clearance after Cimetidine Administration—Is It Useful in the Monitoring of the Function of Transplanted Kidney?

Background. Determination of clearance of endogenous creatinine using its plasma and urinary concentration (standard clearance), Cockroft and Gault formula, or MDRD formula (estimated clearance) is commonly performed for assessment of glomerular filtration rate. Although the evaluation of renal function in this way is useful, it is biased with an error resulting from secretion of creatinine in tubules. This error can be reduced by determining the clearance after administration of cimetidine, which competitively blocks creatinine tubular transport. Methods. The study was performed in the group of 87 patients after renal transplantation. In this group, estimated clearance and creatinine clearance after cimetidine administration (1000 mg in 75 patients and then 1600 mg in 12 patients with plasma creatinine above 3 mg/dL) were determined. Results. Analysis of mean percentage differences between clearance values after cimetidine administration and estimated clearance shows increasing contribution of creatinine tubular secretion along with plasma creatinine increase in renal transplant recipients. A higher dose of cimetidine resulted in lower clearance values in renal transplant recipients with plasma creatinine above 3 mg/dL. Conclusions. Creatinine clearance after administration of 1000 mg cimetidine seems to be a useful measure of glomerular filtration rate in renal graft recipients with plasma creatinine concentration below 2.5 mg/L. Higher dose of cimetidine would be needed to effectively block tubular excretion at higher concentrations of creatinine. Establishing an efficient but safe dose of cimetidine for such patients needs further investigations. As we have noticed that creatinine clearance calculated according to MDRD formula was similar to the clearance after administration of cimetidine, we propose a strategy of one GFR measurement at baseline using 24h urine collection after cimetidine administration and follow-up with creatinine clearance calculated from MDRD formula during standard check-up visits.     

The effect of endothelin antagonists on renal ischaemia-reperfusion injury and the development of acute renal failure in the rat.

BACKGROUND:It is recognized that endothelins are released in response to hypoperfusion and anoxia of the kidney and may be responsible for the consequent deterioration in renal function. This study examined the ability of a non-selective (SB209670) and ET(A)-selective (UK-350,926) endothelin antagonist to attenuate ischaemia-induced renal failure in unilaterally nephrectomized rats. METHODS:The animals were anaesthetized, drug infusion commenced, and the renal artery occluded for 30 min. The endothelin antagonists were given for 30 min before, during, and 60 min after the ischaemic period, at 10, 30 and 100 micro g/kg/min or for 60 min after the start of reperfusion. RESULTS:On day 1, following 30 min renal artery occlusion, there was a 95% reduction in glomerular filtration rate, an 8-10-fold increase in plasma creatinine, and 10-15-fold increases in fractional excretions of sodium and potassium, which were partially resolved on day 3 and normalized on day 8. The lowest dose of SB209670 was without effect on the renal functional responses but they were blunted (all P<0.05) by the highest dose. At 30 and 100 micro g/kg/min UK-350,926, the decreases in renal function subsequent to the ischaemic challenge were attenuated. Administration of UK-350,926 at 100 micro g/kg/min for 1 h starting 60 min after the start of reperfusion, had no effect on the magnitude of the renal disturbances over the first 3 days. CONCLUSIONS:The data show that both the ET(A)/ET(B) and selective ET(A)-receptor antagonist ameliorated the ischaemia-reperfusion injury when given in the peri-ischaemic period but not when the ET(A)-receptor antagonist was given for 60 min at 100 micro g/kg/min after the ischaemic period.     

Renal sodium handling in children with nephrotic relapse: relation to hypovolaemic symptoms

We studied renal sodium handling during water diuresis in childrenin the early phase of relapse of minimal lesion nephrotic syndrome(MLNS). Findings were related to presence or absence of symptomssuggestive of hypovolaemia, and to neurohumoral factors, andwere compared to results of similar studies in the same childrenin remission. Nine children (aged 7.8±3.1 years) presentedwith hypovolaemic symptoms, and 10 (7.4±4.3 years) withoutsuch symptoms. Both groups displayed severe proteinuria, hypoproteinaemiaand oedema. Symptomatic patients showed tendency for a low glomerularfiltration rate, and significantly impaired urine dilution,decreased fractional sodium and lithium excretions, and elevateddiluting segment reabsorption [C_H2O/(C_H2O+C_Na)] and sodium/potassiumexchange [U_K/(U_K+U_Na)]. In the non-symptomatic patients theseparameters were normal. Plasma renin and aldosterone were significantlyelevated in the symptomatic children, and strongly correlatedwith all parameters of tubule sodium reabsorption. Weaker associationswere found for plasma noradrenaline and atrial natriuretic peptide.Vasopressin was also relatively high in the symptomatic group,but showed no association with impaired urine dilution. Thediffusely stimulated tubular sodium reabsorption in the symptomaticchildren, in association with stimulated neurohumoral factors,indicates that secondary sodium retention contributes to oedemaformation in at least a subset of children developing a nephroticrelapse. This may be limited to the early stage, and be morepronounced in some patients than in others. The tubular defectresponsible for maintenance of oedema in stabilized MLNS remainsunclear.     

Anionic and cationic drug secretion in the isolated perfused rat kidney after neonatal surgical induction of ureteric obstruction

OBJECTIVE: To study the pathophysiological changes of renal tubular drug transport mechanisms in congenital renal obstruction, by developing a model for perfusing the isolated kidney (IPK) after neonatal surgical induction of partial ureteric obstruction in Hanover Wistar rats. MATERIAL AND METHODS: Moderately severe obstruction of the right kidney of male rats was created by burying a segment of the right ureter under the psoas fascia at 5-7 days after birth. Different fluorescent substrates for renal organic anion and cation drug transport systems were added to the IPK, and the concentration of these substances with time analysed in perfusate and urine. RESULTS: The reproducibility in all groups of the glomerular filtration rate (GFR) and drug excretion was remarkably good. GFR was significantly lower in obstructed kidneys than in unobstructed kidneys. 123Rhodamine, a marker for organic cation and P-glycoprotein transport, had a significantly lower maximum excretion rate in the obstructed than in unobstructed kidneys. Renal fractional clearance (123rhodamine clearance corrected for diminished GFR) was also significantly lower in obstructed kidneys. There was no significant difference in maximum excretion (absolute and corrected GFR) for Lucifer Yellow, a marker for sodium-dependent organic anion transport. The maximum excretion rate of calcein, a marker for sodium-independent organic anion transport, was significantly lower in the obstructed than in the unobstructed kidneys, but significantly higher after correcting for reduced GFR. CONCLUSION: The IPK is a good model for studying the effect of neonatal renal obstruction on tubular drug transport. These results show that organic anion and cation transport mechanisms are affected differently by obstruction.     

Anaphylaxis following administration of intravenous methylprednisolone sodium succinate in a renal transplant recipient

Methylprednisolone sodium succinate (MPS) is widely used in the management of renal transplantation. Of interest is the rare occurrence of anaphylaxis and anaphylactoid reaction to MPS. We report on a patient who developed anaphylaxis following the intravenous administration of MPS during a renal transplant operation. Intracutaneous testing was carried out with MPS and a strong positive reaction was observed. Histamine and tryptase concentrations were high after the anaphylactic reaction. Including the present case, there have been 13 reports of anaphylactic or anaphylactoid reactions to MPS, occurring in renal transplant recipients. Clinicians should be aware of the potential risk of MPS administration. If transplant patients undergo skin testing against MPS prior to transplant, they may benefit from an alternative medication with other corticosteroids. To use MPS without severe adverse reactions, lower administration rates and dosages are very important.     

Increased cytosolic free sodium in platelets from patients with early-stage chronic renal failure

Cytosolic free sodium concentration ([Na⁺]i) and sodium transportsystems were measured in intact platelets from 19 patients withearly-stage chronic renal failure and 33 healthy control subjectsusing the novel fluorescent dye sodium-binding-benzofuran-isophthalate.Resting [Na⁺]i was significantly greater in patients with chronicrenal failure compared to control subjects (40.8±3.1mmol/1versus 32.2±2.0 mmol/1, mean±SEM, P<0.05).After inhibition of Na-K-ATPase by 1 mmol/1 ouabain a highernet sodium influx was observed in platelets from patients withchronic renal failure compared to control subjects (49.8±8.7mmol/1 versus 28.5±5.2 mmol/1, P<0.05). The plateletNa-H exchanger was similar in the two groups. Cytosolic freecalcium concentration ([Ca²⁺]i) was measured using fura2 anddid not show significant differences between the two groups.To evaluate whether a circulating factor may be associated withelevated [Na⁺]i, a linked-enzyme Na-K-ATPase assay was included.Compared to control subjects plasma from patients with chronicrenal failure produced a significant inhibition of steady-stateNa-K-ATPase activity by 11.2±3.0% (P<0.01). It isconcluded that early-stage renal failure is associated withsignificant impairment of platelet sodium metabolism.     

Acute renal failure after the use of angiotensin-converting-enzyme inhibitors in patients without renal artery stenosis.

During a 4-year period, acute renal failure was observed in 27 patients (mean age 65 years) treated by various angiotensin-converting-enzyme (ACE) inhibitors for hypertension, heart failure, or a combination of both. None had significant renal artery stenosis on angiography. Overt volume depletion was present in 21 and hypotension in 12 cases. All patients received diuretic therapy and/or a low-salt diet. Other facilitating factors included cardiac failure, pre-existing chronic renal insufficiency, combined therapy with non-steroidal anti-inflammatory drugs, and diabetes mellitus. Twenty-two patients had two or more of these factors at presentation. A renal biopsy performed in 10 cases showed severe arteriosclerosis of small renal arteries in eight and acute tubular necrosis in five instances. Therapy comprised volume expansion, and withdrawal of diuretics and, except in two patients, of ACE inhibitors. Twenty-one patients recovered normal renal function, two died, and permanent renal damage remained in four. These results suggest that sodium depletion has a critical role in inducing acute renal failure, whose outcome is not always benign. A combination of diuretics and ACE inhibitors should be prescribed with caution, especially in older patients with small as well as with large renal vessel disease.     

Significance of renal function in changes in acid–base metabolism after orthotopic bladder replacement: Colon neobladder compared with ileal neobladder

BACKGROUND: The objective of this study was to determine whether renal function influences the acid-base metabolism in patients undergoing orthotopic bladder replacement using intestinal segment. METHODS: Acid-base balance, serum electrolytes and renal function were studied in 30 patients with colon neobladder and 18 patients with ileal neobladder. Mean follow up was 51 months. Effects of renal function on acid-base metabolism in both types of bladder replacement were compared. Therapeutic efficacy of the sodium bicarbonate administration was also evaluated in cases with hyperchloremic acidosis. RESULTS: No significant differences were observed in any of the variables examined between the colon and ileal neobladder groups, except for potassium concentration. Although metabolic acidosis was detected using the Siggard-Anderson acid-base nomogram in eight (26.7%) and seven (38.9%) patients in the colon and ileal neobladder groups, respectively, this difference was not significant. In both the colon and ileal neobladder groups, the serum creatinine concentrations in patients diagnosed with metabolic acidosis were significantly higher than in those diagnosed with a normal metabolic status. Furthermore, as a result of severe metabolic acidosis, three (10.0%) and three (16.7%) patients in the colon and ileal neobladder groups, respectively, were administered sodium bicarbonate and their metabolic status was fully normalized. CONCLUSIONS: Despite there being no statistical difference, patients with ileal neobladder may more easily develop metabolic acidosis compared with those with colon neobladder. In addition, a close association between the serum creatinine level and the degree of metabolic acidosis was observed in both groups. However, even if severe metabolic acidosis occurs, it is relatively easy to correct using sodium bicarbonate. These findings suggest that it might be safe to use a colon segment for orthotopic bladder reconstruction in patients with higher serum creatinine levels, despite no significant difference in acid-base metabolism and detection rates of metabolic acidosis between the colon and ileal neobladder groups.     

Dietary potassium and laxatives as regulators of colonic potassium secretion in end-stage renal disease.

BACKGROUND: In end-stage renal disease (ESRD), colonic potassium (K+) secretion increases as renal K+ excretion declines. The nature of this adaptive process is poorly understood, but post-prandial increases in plasma K+ concentration may be a determining factor. In addition, even though colonic K+ secretion increases in ESRD, interdialytic hyperkalaemia is a serious problem in haemodialysis patients, which might be reduced by stimulating colonic K+ secretion still further using laxatives. METHODS: Plasma K+ concentrations were measured in the fasting state, and for 180 min after the oral administration of 30 mmol of K+ to nine control subjects and 16 normokalaemic patients with ESRD (eight "predialysis" patients and eight patients undergoing continuous ambulatory peritoneal dialysis (CAPD)). Plasma K+ concentrations were also monitored for 180 min in fasting controls and ESRD patients who were not given the oral K+ load. To study the effect of laxatives on interdialytic hyperkalaemia, plasma K+ concentrations were measured in eight control subjects and 13 haemodialysis patients before and during 2 weeks treatment with bisacodyl (a cAMP-mediated laxative) and in five haemodialysis patients before and during 2 weeks treatment with lactulose (an osmotic laxative). RESULTS: Oral K+ loading caused plasma K+ concentration to rise within the normal range (3.5-5.1 mmol/l) in control subjects, while significantly higher concentrations were achieved in the "predialysis" patients and sustained hyperkalaemia developed in the CAPD patients. Bisacodyl treatment had no effect on plasma K+ concentrations in control subjects, but significantly decreased the mean interdialytic plasma K+ concentration (from 5.9+/-0.2 to 5.5+/-0.2 mmol/l, P<0.0005) in haemodialysis patients, whereas plasma K+ concentration did not change during lactulose treatment. CONCLUSIONS: Higher plasma K+ concentrations after food may help to maintain K+ homeostasis in ESRD by enhancing colonic K+ secretion. Bisacodyl may be useful for reducing interdialytic hyperkalaemia in patients undergoing haemodialysis.     

Nateglinide improves postprandial hyperglycemia and insulin secretion in renal transplant recipients

BACKGROUND: Postprandial hyperglycemia (PPHG) frequently occurs among renal transplant recipients (RTR). Reduced early insulin response (EIR) after a meal leads to impaired suppression of endogenous glucose production and subsequently PPHG, which is a risk factor for cardiovascular disease. Nateglinide is a rapid acting insulin secretagogue inducing an EIR after a meal. Our main objective was to investigate the safety and effect of nateglinide treatment on postprandial plasma glucose excursions and insulin secretion in RTR with PPHG. PATIENTS AND METHODS: A total of 14 Caucasian RTR with new-onset diabetes mellitus (NODM; n = 6) or impaired glucose tolerance (IGT; n = 8) were included. The insulin response and glucose excursions were measured for 240 min after a standardized liquid meal at baseline and after two-wk treatment with nateglinide. RESULTS: Treatment with nateglinide was followed by a significant decrease in mean two-h plasma glucose from 10.5 mmol/L (3.1) to 7.6 mmol/L (2.1; p < 0.001) and a decline in total postprandial area under the curve (AUC) of glucose concentration (p < 0.001). Both estimated EIR and the late insulin response increased significantly (p = 0.008 and p = 0.003, respectively). No serious adverse event was observed during the study period. CONCLUSIONS: Treating RTR with nateglinide for two-wk significantly improved PPHG, increased the insulin response following a standardized meal and was well tolerated.