Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.     

Renal functional reserve in children with reduced renal mass: study by two dietary periods

It has been suggested that the renal functional reserve (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (C _in) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dictary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3–4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%–139%) RDA for the LP period and 220% (163%–319%) RDA for the HP period.C _in did not change in 14 children with GFR below (n=7) or within (n=7) the normal range.C _in was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m². Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.     

Renal functional reserve after acute poststreptococcal glomerulonephritis

 We evaluated renal functional reserve (RFR) in 36 patients aged 5 – 21 years, who had recovered from an acute episode of poststreptococcal glomerulonephritis (PSGN) 1 – 16 years previously, without apparent sequelae, as evidenced by normal serum creatinine, blood pressure, and urinary sediment. The control group consisted of 12 children aged 2 – 12 years with recurrent urinary tract infections or nocturnal enuresis, without active infection or anatomical anomalies. The basal creatinine clearance was similar in the PSGN and control groups: 140.0±27.4 ml/min per 1.73 m² and 142.9±15.5 ml/min per 1.73 m², respectively. The RFR in the PSGN group was significantly reduced compared with that of the control group: 18.6±12.9 ml/min per 1.73 m² and 41.1±25.3 ml/min per 1.73 m², respectively (P <0.02). In 7 PSGN patients (19.4%), no RFR was found. In 69% of patients who had recovered from PSGN more than 10 years before the protein loading tests, a significantly reduced RFR (less than 10% of baseline) was found. The same degree of reduction in RFR was found in only 26% of patients who had suffered from PSGN less than 10 years ago. Received May 23, 1996; received in revised form November 11, 1996; accepted November 27, 1996     

Renal functional reserve in children with a previous episode of haemolytic-uraemic syndrome

Renal function [creatinine clearance (C _Cr)] and renal functional reserve (RFR) was measured in 16 children who had had haemolytic-uraemic syndrome (HUS) an average of 6.6±0.72 years previously. All patients had normal plasma creatinine and blood pressure and only 3 had proteinuria, which was mild in every instance. Patients were studied whilst ingesting three diets which provided an average of 1.5, 2.1 and 3.1 g protein/kg body weight per day, respectively. Diets were administered over three consecutive periods of 7 days each andC _Cr was measured on the 7th day of each diet. Values tended to correlate with protein intake. They were in the normal range when patients were taking 1.5 and 2.1 g protein diets and increased markedly in 13 of the 16 patients (P<0.001) when they ingested the high-protein diet (3.1 g). The effect on glomerular filtration rate (GFR)-measured byC _Cr and inulin clearance (C _in)-of an acute oral protein load was studied in 12 of the HUS patients and four control subjects. In the control periods, prior to the protein load, values forC _Cr were similar in the HUS and control subjects (104.0±11.0 vs 121.6±10.1 ml/min per 1.73 m², NS). HoweverC _in values were significantly reduced in HUS patients (59.5±9.2 vs 102.7±12.4 ml/min per 1.73 m², (P<0.025). TheC _Cr/C _in ratio in the patients averaged 2.10 compared with 1.13 in controls. Acute protein loading was accompanied by an increase inC _in in all controls but in only 8 of the 12 patients. Baseline values forC _in did not correlate with the presence or absence of protein-stimulated enhancement ofC _in. TheC _Cr/C _in ratios after protein loading remained twice as high in HUS patients as in controls. The data indicate thatC _Cr is not an accurate indicator of GFR in children who have had acute renal injury. Tubular secretion of creatinine represents a greater proportion of excreted creatinine in these children, may maintain serum creatinine in the normal range and mask the decrease in GFR. The study also emphasizes the problems of measuring RFR in these children.     

Renal functional reserve in transplanted and native single kidneys of children and adults

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23%±3%, 20%±3% and 15%±3% in Tx, Don, and Nx/Ag and RFR ERPF 35%±4% in Tx, which was significantly higher than 20%±4% and 15%±3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity. Received September 19, 1995; received in revised form September 16, 1996; accepted October 1, 1996     

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.     

Shor- and long-term effect of a calcium channel blocker, barnidipine, on renal hemodynamics in spontaneously hypertensive, diabetic rats

Background The purpose of this study was to examine the short- and long-term effects of the calcium channel blocker, barnidipine, on renal hemodynamics and urinary albumin excretion in spontaneously hypertensive rats with streptozotocin-induced diabetes. Methods Diabetic and nondiabetic spontaneously hypertensive rats and nonhypertensive rats were treated with barnidipine or placebo (vehicle). In the short-term experiment, barnidipine was given as a single bolus injection (3 μg/kg); in the long-term experiment, barnidipine was administered orally (15 mg/kg per day) for 16 to 20 weeks. Results Renal hyperfiltration was observed in both hypertensive and nonhypertensive rats at 1 to 2 weeks after induction of diabetes, without changes in renal blood flow. Although short-term administration of barnidipine significantly decreased mean arterial pressure and renal vascular resistance, barnidipine did not affect renal blood flow or glomerular filtration rate in hypertensive, diabetic rats. At 16 to 20 weeks after induction of diabetes, renal hyperfiltration and increased urinary albumin excretion were still observed in hypertensive rats given placebo, compared to values for hypertensive nondiabetic rats given placebo. Long-term administration of barnidipine to hypertensive, diabetic rats suppressed the increase in both glomerular filtration rate and urinary albumin excretion, and reduced systolic blood pressure without any change in renal blood flow, renal vascular resistance, or filtration fraction. Conclusions These results indicate that in hypertensive, diabetic rats short-term administration of barnidipine, despite reducing renal vascular resistance, is less effective than long-term administration in restoring normal renal filtration, although long-term administration may normalize renal filtration and reduce urinary albumin excretion.     

Renal revascularization in high-risk patients: The role of iliac renal bypass

Between 1984 and 1989, 29 iliac renal artery bypasses were performed in 29 patients (mean age 67.8 years) with severe renovascular disease due to atheroma. The indication for renal artery reconstruction was hypertension in all patients, which was associated with kidney failure in 16 cases. In six cases, reconstruction was performed after failure or complications of percutaneous transluminal angioplasty. The bypass was constructed with polytetrafluoroethylene in 24 cases (83%) and vein graft in five cases (17%). There was no postoperative mortality. All bypasses were found to be patent on duplex scanning or digital subtraction arteriograms. One patient was lost to follow-up. Mean follow-up was 23.2 months. One patient died of acute kidney failure, probably related to occlusion of the bypass. Hypertension improved in 22 cases (79%), was cured in two cases (7%), and remained unchanged in four (14%). Renal function remained unchanged in six cases (40%) and improved in nine (60%). Iliac-to-renal artery bypass seems to be the surgical renal revascularization modality best adapted to high-risk patients or those who have severe atheroma. Additionally, this technique enables rapid treatment of failures or complications of percutaneous transluminal angioplasty of the renal artery.Presented at the Annual Meeting of the Société de Chirurgie Vasculaire de Langue Française, May 18–19, 1990, Nancy, France.     

Do ultrasound renal resistance indices reflect systemic rather than renal vascular damage in chronic kidney disease?

BACKGROUND: In patients suffering from chronic kidney disease (CKD), ultrasound renal resistance indices predict progression of kidney disease and death. Although ultrasound resistance indices were initially considered to directly reflect intrarenal vascular resistance, they are complex composite parameters that are influenced by various vascular factors. We hypothesized that renal resistance indices reflect systemic vascular disease rather than local renal damage in patients with CKD. METHODS: In 140 patients suffering from CKD not receiving renal replacement therapy, intrarenal resistance indices were measured in interlobar arteries. For assessment of systemic atherosclerotic disease, common carotid intima-media thickness (IMT) and ankle-brachial blood pressure index were determined. Categories of risk for coronary heart diseases were defined by Framingham risk scoring. RESULTS: Increased renal resistance indices were associated with high Framingham risk scores and with the presence of atherosclerotic disease. In addition, ultrasound renal resistance indices progressively increased with the stage of renal function impairment, and patients suffering from diabetic nephropathy had higher resistance indices than patients suffering from other renal diseases. In a multivariate linear regression analysis, IMT, Framingham risk score, renal function, presence of diabetic nephropathy and pulse pressure independently predicted resistance indices. However, when additionally adjusting for age, IMT and Framingham risk score were no longer independent predictors of resistance indices. CONCLUSIONS: In patients suffering from CKD, intrarenal resistance indices are independently associated with cardiovascular risk score and systemic vascular disease as well as with aetiology and stage of CKD. This may explain their strong association with both impaired renal outcome and death.     

Coffee,nutritional status,and renal artery resistive index

Background: The relationship between nutrition and atherosclerosis is known, even dissociated from protein malnutrition. Cardiovascular impact of several nutrients is known; among them the action of coffee is still debated and cardiovascular effect of caffeine has been investigated without definite results. Objective: The aim of this study is to investigate whether coffee habits, and/or quantity of coffee consumption, have any relationship with renal resistive index (RRI), a hallmark of arterial stiffness (AS). The relationship of AS with nutritional status assessed by body composition and serum albumin, insulin resistance (assessed by HOMA), and renal function assessed by glomerular filtration rate (GFR) is concurrently investigated. Methods: This study was done with 221 consecutive patients, without diabetes, cancer, liver, renal, and heart disease, referred for clinical noninvasive assessment and nutritional counseling: 124 essential hypertensive and 97 nonhypertensive patients were eligible. Personalized Mediterranean diet, physical activity increase, and smoking withdrawal counseling were provided. Results: By multiple linear regression, fat-free mass (FFM), HOMA (positive relationship), and number of cups of coffee/day (negative relationship) account for 17.2% of the variance to RRI. By odds ratios lower risk to increased RRI is associated with higher serum albumin, higher hemoglobin, and FFM; greater risk is associated with hypertension, insulin resistance (HOMA ≥ 3.0), and renal insufficiency (GFR ≤ 90); coffee, assessed by number of cups/day, reduces risk. Conclusion: Coffee use is inversely associated with RRI. Habitual coffee users have risk protection to higher RRI; lower serum albumin, insulin resistance, and renal insufficiency are associated with greater RRI.     

Renal effects of rapamycin in the spontaneously hypertensive rat

The effects of rapamycin (RAPA), administered at therapeutic doses, were investigated in the spontaneously hypertensive rat (SHR). Additionally, the reversibility of RAPA's renal effects was investigated at a supratherapeutic dose. At doses that were active in preventing heart and kidney allograft rejection in the rat (0.01–0.08 mg/kg i.v.), RAPA had no effect on kidney function or rat body weight gain. At higher doses (0.8 mg/kg), RAPA produced significant changes in kidney function parameters and caused a loss in body weight. Histopathologic changes, including necrotizing vasculopathy and tubular atrophy, were noted at therapeutic doses. The effects of RAPA on kidney function were completely reversible after a 2-week washout period, though the histopathologic changes were still evident. These studies demonstrate that RAPA does not impair kidney function at therapeutic doses when administered for 2 weeks but does appear to accelerate the naturally occurring renal lesions of the SHR.     

Renal and systemic effects of continued treatment with renin inhibitor remikiren in hypertensive patients with normal and impaired renal function.

BACKGROUND: Remikiren is an orally active renin inhibitor with established antihypertensive efficacy. As a single dose it induces renal vasodilatation, suggesting specific renal actions. Data on the renal effects of continued treatment by renin inhibition are not available, either in subjects with normal, or in subjects with impaired renal function. METHODS: The effect of 8 days of treatment with remikiren 600 mg o.i.d. on blood pressure, renal haemodynamics, and proteinuria was studied in 14 hypertensive patients with normal or impaired renal function.The study was conducted on an ambulatory in-hospital basis and was designed in a single-blind, longitudinal order. RESULTS: Remikiren induced a significant peak fall in mean arterial pressure of 11.2+/-0.8%, with corresponding trough values of -6+/-0.8%. This fall was somewhat more pronounced in the patients with renal function impairment (-13.3 vs -9.6%; P<0.01). Glomerular filtration rate remained stable, whereas effective renal plasma flow increased from 301+/-35 to 330+/-36 ml/min/1.73 m(2) (P<0.05). Filtration fraction and renal vascular resistance fell by 10+/-2% and 15+/-2% respectively (both P<0.01). Remikiren induced a cumulated sodium loss of -82+/-22 mmol and a positive potassium balance of 49+/-9 mmol (both P<0.01). During remikiren, proteinuria fell by 27% (range -18 to -38%; P<0.01) in the patients with overt proteinuria at onset (n=6). In the remainder of the patients albuminuria fell by 20% (range -1 to -61%, P<0.05). No side-effects were observed. CONCLUSIONS: Continued treatment with remikiren induced a sustained fall in blood pressure, renal vasodilatation, negative sodium balance, and a reduction in glomerular protein leakage. These data are consistent with a renoprotective potential of renin inhibition.     

The effect of diuretics on systemic and renal hemodynamics in patients with renal insufficiency

Diuretics have been used in acute renal failure in an attempt to increase urine flow and ameliorate the reduction in glomerular filtrate rate. A beneficial response occurs in some experimental models of acute renal failure when diuretics are administered prophylactically or very early in the course of renal failure and may require a renal vascular bed capable of responding partially, at least, to vasodilating stimuli. In chronic renal insufficiency the most important indications for diuretic use are for the treatment of systemic hypertension and for the correction of the congested state. However, the precise effect of diuretic therapy under these conditions is unpredictable and dependent on the functional state of the renal vessels. Diuretic administration may at times prove detrimental, resulting in a deterioration of glomerular filtration rate. In hemodynamically unstable conditions the slow removal of extracellular fluid by continuous arteriovenous hemofiltration may prove preferable to diuretic administration or standard forms of dialysis.     

Renal hemodynamic changes and renal functional reserve in children with type I diabetes mellitus

Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with type 1 diabetes mellitus to assess whether hyperfiltration occurs. The renal hemodynamic response following dopamine infusion was examined in 51 normoalbuminuric diabetic children (7.7 ± 3.6 years) with a mean duration of diabetes of 6.2 years and compared them with 34 controls. Mean baseline GFR in diabetic children did not differ from the control population (130.7 ± 22.9 vs. 124.8 ± 25 ml/min per 1.73 m²), whereas renal plasma flow was significantly lower (463.7 ± 103.9 vs. 587.2 ± 105 ml/min per 1.73 m², p < 0.001), and filtration fraction was increased (29 ± 8 vs. 21 ± 2%, p < 0.001), compared with controls. The mean RFR was lower (p < 0.001) than in control subjects (−0.77 ± 23 vs. 21 ± 8 ml/min per 1.73 m²). This study documents an increased filtration fraction and reduced or absent RFR in children with type 1 diabetes mellitus in the stage before apparent nephropathy. GFR values were within normal range. Although the reduced RFR and increased filtration fraction indicate the presence of hemodynamic changes, their relevance to the development of hyperfiltration and subsequent diabetic nephropathy remains unknown.     

肝癌患者术前肝脏储备功能的综合评估

肝切除是目前治疗肝癌患者最有效的方法.在我国约80%的肝癌患者伴有不同程度的肝硬化.肝硬化患者的肝组织再生能力差,储备功能降低,肝癌合并肝硬化患者接受肝切除手术将面临更大的风险,术后主要死因是肝功能衰竭,因此,必须重视术前肝脏储备功能的评估.本文主要对肝癌患者术前肝脏储备功能的综合评估进行综述.     

An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: comparisons with human hypertensive nephropathy.

Urinary excretion of tissue kallikrein is reduced in essential hypertension. Although a similar finding has been reported in spontaneously hypertensive rats (SHR), only a few studies have been concerned with the amount of enzyme within the kidney both at the time of onset and during progression of the hypertension. We have performed an ontogenic study on the renal parenchymal values and immunoreactivity of tissue kallikrein in Okamoto SHR aged 4-78 weeks. Additionally, these two parameters were analysed in human biopsies taken from patients with hypertensive nephropathy. The enzymatic activity of renal tissue kallikrein (active and total; specifically antagonized by anti-tissue kallikrein antibodies), increased from 4 to 52 weeks in SHR when compared to normotensive Wistar Kyoto (WKY) rats; this increase was associated with a significant increase in blood pressure. In contrast, 78 weeks SHR and human biopsy tissue showed a substantial reduction in tissue kallikrein values. Also, both renal tissues showed a reduction in immunoreactivity in the cells of the connecting tubules that specifically store the enzyme. In advanced hypertension the observed reduction in tissue kallikrein was probably secondary to a loss of distal tubular mass, as a result of tubular atrophy and fibrosis. The greater values for renal tissue kallikrein in the kidney and reported reduced urinary excretion during the early phases of spontaneous hypertension may be explained by a primary defect in the mechanisms that regulate release of tissue kallikrein from the connecting tubule cells.     

Significance of the Renal Functional Reserve in Reflux Nephropathy: An Evaluation According to the Degree of Glomerular Damage

Objective. In the treatment of progressive reflux nephropathy (RN), the therapeutic benefit and prognosis of the renal function in RN patients appears to be influenced by the degree of renal functional reserve. We designed this study to determine the presence and characteristics of the renal functional reserve in RN patients. Materials and Methods. In the 35 RN patients with renal scars (19 males; mean age 16.1 years), an exogenous renal clearance test was performed to measure the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF). In the second half of this test, the renal functional reserve was estimated by measuring the GFR and ERPF during low-dose dopamine infusion. These measurements were then compared with the glomerular size, which had been previously determined by a renal biopsy. Results. Among the patients with a normal glomerular size (?2SD to +2SD), the GFR markedly increased after low-dose dopamine infusion (from 112.15 ± 52.51 to 182.07 ± 69.95mL/min, p < 0.0001), whereas an increase in ERPF was not significant. Among the patients with an enlarged glomerular size (+2SD to +4SD), the GFR and ERPF increased significantly over the baseline values (from 54.60 ± 32.90 to 114.00 ± 65.48 mL/min, p = 0.0076; from 281.01 ± 152.54 to 622.43 ± 392.73 mL/min, p = 0.0155, respectively). Among the patients with an extremely enlarged glomerular size (>+4SD), both the GFR and ERPF remained almost completely unchanged. Conclusion. The renal functional reserve was present even among progressive RN patients with a glomerular size ranging between +2SD and +4SD.     

The evaluation of renal hemodynamics changes in Familial Mediterranean fever with color Doppler sonography

Background: Renal resistive index (RRI) scanned through renal Doppler is a practical marker employed in measuring blood flow in renal and intrarenal arteries and in noninvasive evaluation of renal vascular resistance. We aimed to investigate the renal hemodynamic variations in patients with Familial Mediterranean Fever (FMF).

Material and methods: Seventy-nine FMF patients and 51 healthy subjects suitable for age and sex were included. Patients were divided into two groups according to their urinary albumin excretion. Fifty-two patients with 0–29?mg/day albuminuria were included in the normoalbuminuric group while 27 patients with 30–299?mg/day albuminuria were included in the microalbuminuric group.

Results: RRI values were higher in patients with FMF compared to the healthy subjects (p?p?=?0.002, p?p?=?0.013.

Conclusion: RRI may be a marker that may be used in assessing resistance to renal blood flow, early renal damage, and progression of renal damage in FMF patients.     

MELD评分评估肝硬化肝功能储备力的临床研究

目的准确评估肝储备功能可大大促进肝胆外科的发展，本实验旨在通过MELD评分与Child-Pugh分级及肝纤维化定量评估间关系的研究，了解MELD评分系统对评估肝硬化病人肝功能储备力的价值。方法通过对19例正常对照组和23例肝炎后肝硬化肝病组病人术前测定MELD评分，同时采用计算机辅助数字图像分析法检测正常对照组和肝病组病人肝组织标本的纤维化程度，分析MELD评分与Child-Pugh分级及肝纤维化定量评估间的关系。结果肝硬化病人MELD评分与肝纤维化面积百分比间呈正的直线相关关系（r=0．84，P〈0．01），Child A、B、C三组间MELD评分亦具有显著性差异（P〈0．01）。结论MELD评分是评估肝硬化病人肝储备功能的较好方法。