24-hour Urinary Protein Excretion Research Articles

ENDOTHELIAL FUNCTION OF CONDUIT AND RESISTANCE ARTERIES IN NEPHROTIC RANGE PROTEINURIA

OBJECTIVE: To test the hypothesis that endothelial dysfunction occurs in nephrotic range proteinuria primarily as a consequence of dyslipidaemia. METHODS: Brachial artery and forearm microcirculatory endothelial function was compared among patients with nephrotic range proteinuria (NRP, n = 14 ), primary hyperlipidaemia (HL, n = 15) and normal controls (NC, n = 16). Endothelial function was studied by measuring post-ischaemic flow-mediated dilatation (FMD) of the brachial artery using high resolution ultrasonography. Endothelium-independent, glyceryl trinitrate (GTN) mediated brachial artery vasodilatation was also measured. Basal and post-ischaemic blood flow of the forearm microcirculation was measured using venous-occlusion strain gauge plethysmography. RESULTS: Serum creatinine was similar among groups. The proteinuric group had a mean albumin of 27.6g/L(1.8) and 24-hour urinary protein excretion of 6.3g(1.3). Plasma lipids and lipoproteins were not statistically different between the NRP and HL groups. Brachial artery FMD was significantly lower in the NRP and HL groups compared with the controls (NRP 4.7%(1.3)*, HL 4.9%(0.7)* and NC 8.3%(0.6), *p = 0.012 vs. NC); GTN mediated dilatation and basal and post-ischaemic forearm blood flow were not statistically different among the three groups. CONCLUSION: Patients with nephrotic range proteinuria have endothelial dysfunction of conduit arteries in the peripheral circulation, similar to that observed in patients with primary hyperlipidaemia. This suggests dyslipoproteinaemia is the principal cause of endothelial dysfunction of conduit arteries in nephrotic range proteinuria. Confirmation of this should be sought with an intervention trial of lipid-regulating therapy.

Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension.

To determine whether hormone replacement therapy can reverse established renal microvascular damage in type 2 diabetes and hypertension. Prospective, single centre clinical trial. Outpatient clinics. Sixteen diabetic and hypertensive postmenopausal women (age 47-57 years) Administration of a cyclic combination of oestradiol and norgestrel orally for 3.5 monthly cycles. Comparing the baseline values, mean (SD) 24-hour urine protein excretion was reduced from 0.452 g (0039) to 0.370 g (0.047) (P < 0.01) and creatinine clearance was increased from 1.68 mL/sec (0.11) to 1.77 mL/sec (0.08) (P < 0.05). Fasting plasma glucose also improved from 6.92 mmol/L (0.47) to 6.51 mmol/L (0.28) (P < 0.05), as did serum total cholesterol from 7.26 mmol/L (0.28) to 6.65 mmol/L (0.14) (P < 0.05). Blood pressure did not change significantly. Univariate linear regression analysis showed no significant correlation between the individual changes in blood pressure, fasting plasma glucose or serum cholesterol and the individual changes in proteinuria or creatinine clearance. This study shows that hormone replacement therapy may reduce proteinuria, and even improve creatinine clearance, in diabetic and hypertensive postmenopausal women. These effects are additive to nephroprotective therapy, and the mechanisms appear unrelated to conventional risk factors for vascular complications, such as high blood pressure, elevated plasma glucose or serum cholesterol.

Endothelial function of conduit and resistance arteries in nephrotic range proteinuria

OBJECTIVE: To test the hypothesis that endothelial dysfunction occurs in nephrotic range proteinuria primarily as a consequence of dyslipidaemia. METHODS: Brachial artery and forearm microcirculatory endothelial function was compared among patients with nephrotic range proteinuria (NRP, n = 14 ), primary hyperlipidaemia (HL, n = 15) and normal controls (NC, n = 16). Endothelial function was studied by measuring post-ischaemic flow-mediated dilatation (FMD) of the brachial artery using high resolution ultrasonography. Endothelium-independent, glyceryl trinitrate (GTN) mediated brachial artery vasodilatation was also measured. Basal and post-ischaemic blood flow of the forearm microcirculation was measured using venous-occlusion strain gauge plethysmography. RESULTS: Serum creatinine was similar among groups. The proteinuric group had a mean albumin of 27.6g/L(1.8) and 24-hour urinary protein excretion of 6.3g(1.3). Plasma lipids and lipoproteins were not statistically different between the NRP and HL groups. Brachial artery FMD was significantly lower in the NRP and HL groups compared with the controls (NRP 4.7%(1.3)*, HL 4.9%(0.7)* and NC 8.3%(0.6), *p = 0.012 vs. NC); GTN mediated dilatation and basal and post-ischaemic forearm blood flow were not statistically different among the three groups. CONCLUSION: Patients with nephrotic range proteinuria have endothelial dysfunction of conduit arteries in the peripheral circulation, similar to that observed in patients with primary hyperlipidaemia. This suggests dyslipoproteinaemia is the principal cause of endothelial dysfunction of conduit arteries in nephrotic range proteinuria. Confirmation of this should be sought with an intervention trial of lipid-regulating therapy.

Angiotensin II blockade and low-protein diet produce additive therapeutic effects in experimental glomerulonephritis

Transforming growth factor-beta (TGF-beta) overexpression plays a key role in the accumulation of extracellular matrix in acute and chronic renal diseases. Recent studies have suggested that the degree of reduction in pathological TGF-beta overexpression can be used as a therapeutic index to evaluate the antifibrotic potential of pharmacological angiotensin II (Ang II) blockade in renal disease. Using this target, we found that treatment with the angiotensin I-converting enzyme inhibitor enalapril or the Ang II type 1 receptor antagonist losartan reduced TGF-beta overexpression more effectively at doses clearly higher than those required to control blood pressure. However, both forms of Ang II blockade were only partially effective in normalizing TGF-beta expression. This study investigated whether a greater antifibrotic, TGF-beta-reducing benefit can be achieved when Ang II blockade is combined with dietary protein restriction. Mesangioproliferative glomerulonephritis was induced in male Sprague-Dawley rats on a normal-protein diet. Treatment with a low-protein diet and/or maximally effective doses of enalapril or losartan was started one day after disease induction. On the fifth day, 24-hour urine protein excretion was measured. On the sixth day, cortical kidney tissue was taken for periodic acid-Schiff staining. Isolated glomeruli were used for mRNA extraction or were placed in culture for determination of production of TGF-beta1, the matrix protein fibronectin, and the protease inhibitor plasmin activator inhibitor type 1 (PAI-1) by enzyme-linked immunosorbent assay. Compared with untreated nephritic animals on a normal-protein diet, a single treatment with enalapril, losartan, or low-protein diet significantly reduced glomerular TGF-beta production, albeit to a similar degree of approximately 45%. A moderate, but significant further reduction in pathological TGF-beta expression of a total of 65% for enalapril and 60% for losartan was achieved when these drugs were combined with low-protein feeding. This reduction in TGF-beta overexpression paralleled decreased proteinuria, glomerular matrix accumulation, and overproduction of fibronectin and PAI-1. Ang II blockade and low-protein diet have additive effects on disease reduction, suggesting that disease progression in humans with chronic renal failure may be slowed more effectively when Ang II blockade and low-protein diet are combined. Since maximal pharmacological Ang II inhibition was used, it is likely that dietary protein restriction further reduces pathological TGF-beta overexpression by mechanisms different from those of enalapril or losartan.

Renal Findings and Glomerular Pathology in Diabetic Subjects

Background: To describe the relationship between proteinuria, hematuria, and renal insufficiency, on one hand, and glomerular pathology, on the other hand, in a consecutive biopsy series of diabetic patients. Subjects and Methods: All diabetic subjects (n = 200) biopsied from 1979 to 1995 at Tampere University Hospital were identified in retrospect. The clinician-based indication (any unexplained renal finding) for renal biopsy was consistent during the years and was: proteinuria alone in 68%; combined with hematuria in 10%; with renal insufficiency in 10%; with both in 9%, and with isolated hematuria or renal failure in 3%. One third of the subjects had proteinuria of ≧3 g/24 h and 16% a serum creatinine level of ≧200 µM. Glomerulopathy was found in 171 specimens and defined as nodular diabetic (group A), diffuse diabetic (group B) and primary (group C). The 24-hour urinary protein excretion rate [mean (range)] was 3.5 (1.6–6.9), 1.0 (0.5–3.5), and 3.6 (1.1–6.6) g in groups A, B and C, respectively (ANOVA p = 0.001). The corresponding serum creatinine values [mean (SD)] were 175 (115), 105 (142) and 169 (138) µM (p = 0.001). Results: Nodular diabetic glomerulopathy was found in 40%, diffuse diabetic glomerulopathy in 42% and primary glomerulopathy in 18%. A primary glomerulopathy was found in any indication and in both types of diabetes (prevalence range 14–26%). The best multivariate logistic regression model obtained (χ² = 13.5, p = 0.008) in predicting the presence of diabetic glomerulosclerosis (group A + B) in contrast to a primary glomerulopathy (group C) included retinopathy (p = 0.04), renal insufficiency (p = 0.03), hematuria (p = 0.12) and type of diabetes (p = 0.10). Conclusion: In this series of diabetic subjects, biopsied due to proteinuria, hematuria and not severe renal insufficiency, 18% had evidence of a primary glomerulopathy.

Intermittent intravenous cyclophosphamide arrests progression of the renal chronicity index in childhood systemic lupus erythematosus

Objective: To assess prospectively the safety and efficacy of a 36-month course of systematic bolus intravenous cyclophosphamide therapy (IVCY) for children with lupus nephritis. Study design: Sixteen children with lupus nephritis were treated with IVCY for 36 months. Renal biopsies performed before and after treatment were scored for activity and chronicity. SLEDAI scores, laboratory measures, and prednisone dosage were recorded at the time of each treatment. Results: After 36 months of IVCY therapy, the renal biopsy activity index decreased from 9 ± 4 to 1 ± 1 ( P < .001) without a change in chronicity. The mean creatinine clearance increased from 90 ± 23 to 107 ± 23 mL/min/1.73 mol/L 2 ( P < .01), and the mean 24-hour urine protein excretion decreased from 2.0 ± 2.4 g/24 h to 0.5 ± 0.7 g/24 h ( P < .05). The mean SLEDAI score decreased from 19 ± 5.2 to 2.9 ± 3.1 ( P < .001). The mean prednisone dosage decreased from 35.5 ± 20 mg/d to 14.0 ± 3 mg/d ( P < .001). No significant complications occurred. Conclusions: Thirty-six months of systematic IVCY therapy led to decreased renal biopsy activity without progression of chronicity, with excellent disease control and a greater than 50% reduction in mean corticosteroid dose. (J Pediatr 2000;136:243-7)

5/6腎摘ラットにおけるL-ArginineのNO産生および糸球体組織に対する逆説的用量依存性効果

Whether L-Arginine (L-ARG) ameliorates or aggravates renal function and histopathological changes in several models of renal disease remains controversial as L-ARG is the substrate for nitric oxide (NO) synthase as well as the precursor of proline and polyamines which cause renal fibrosis. These ambiguous results might be attributed to differences in the dose and period of L-ARG administration and the animal model used in each observation. Therefore, we tested the dose-dependent effect of L-ARG on mean blood pressure (MBP), 24-hour urinary excretion of protein (UP), NO metabolites (NO2(-) + NO3-) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. These 5/6 nephrectomized SD rats were divided into 4 groups: 1. L-ARG 0.2 g/kg/day (0.2 g ARG), 2. L-ARG 1 g/kg/day (1 g ARG), 3. L-ARG 2 g/kg/day (2 g ARG), 4. No administration of L-ARG(ARG(-)). Compared with ARG(-)MBP, UP and ADMA were significantly decreased and NO2(-) + NO3-, cGMP were significantly increased in the 0.2 g ARG. SI group and %INT were significantly increased in the 2 g ARG group and decreased in the 0.2 g ARG group. A small dose of L-ARG ameliorated glomerulosclerosis and interstitial fibrosis while a larger dose did not. SI, %INT and ADMA were inversely correlated with NO2(-) + NO3-. These data suggested that renal NO synthesis might attenuate glomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decrease in NO.

Rise in serum albumin and creatinine in the first half year on hemodialysis

Rise in serum albumin and creatinine in the first half year on hemodialysis. Serum albumin and creatinine have been reported to rise in new hemodialysis patients; however, these trends have not been quantitated in a stable cohort, and their determinants and prognostic value are unknown. This study examined the changes in monthly values of serum albumin and creatinine over the first half year of hemodialysis in 115 patients who survived to the start of the sixth month. After verifying that the trends were approximately linear, we calculated the rates of rise (slope) of six predialysis values of serum albumin (months 1 through 6) and of creatinine (months 2 through 7) and examined their associations with age, diabetes, race, baseline 24-hour urine protein and creatinine excretion, and survival during the latter half of the first year. Serum albumin rose by 13% over months 1 through 6 [0.08 +/- 0.12 (SD) g/dl/month, P < 10-9 vs. zero slope]. Patients who survived the entire year had higher mean values for both serum albumin (month 1, P < 0.003; months 3 through 6, P < 10-3) and rate of rise of albumin (0.09 +/- 0.11 g/dl/month vs. 0.01 +/- 0.13 g/dl/month, P < 0.005) than patients who died during months 6 through 12, but the slope was not an independent predictor of survival after adjusting for serum albumin concentration. Baseline proteinuria correlated inversely with serum albumin measured at the first and second months (P < 0.005) and directly with the albumin slope (r = 0.49, P < 10-5). Serum creatinine rose by 12% between months 2 through 7 (0.12 +/- 0.47 mg/dl/month, P < 0.02). Survivors had a significantly higher mean baseline creatinine excretion (P < 0. 03) and serum creatinine (month 2, P < 0.03; months 3 through 7, P < 0.01) but only a marginally higher rate of rise of serum creatinine (0.16 +/- 0.47 mg/dl/month vs. -0.07 +/- 0.48 mg/dl/month, P < 0.06) than patients who died during the second half of the year. Baseline urinary creatinine excretion correlated directly with serum creatinine at month 2 (P < 0.01) and more strongly at months 3 through 7 (P < 10-3), as well as correlating with the creatinine slope (r = 0.26, P < 0.03). Serum albumin and creatinine rose by 12 to 13% during the first half year of hemodialysis in a stable cohort. The slope of serum albumin versus time predicted survival, but it was not as predictive as the absolute albumin concentration. The pattern of correlations of baseline urinary protein and creatinine excretion with the respective monthly serum values of albumin and creatinine and their slopes is consistent with the hypothesis that as residual renal function declines, progressive retention of protein and creatinine contributes to the respective rises in serum albumin and creatinine.

Proteinuria is an independent risk factor for ischemic stroke in non-insulin-dependent diabetes mellitus.

Proteinuria is an independent risk factor for cardiovascular disease in patients with NIDDM. The aim of this study was to assess the relationship between proteinuria and ischemic stroke in subjects with NIDDM, and to determine whether proteinuria is an independent risk factor for stroke. We performed a case-control study of 59 diabetic patients with first-ever ischemic stroke due to thrombotic arterial occlusion, who were considered cases, and 180 diabetic patients without stroke, matched by gender, age, and diabetes duration, as a control group. WHO criteria for verified definite or possible stroke were used to ascertain the diagnosis of stroke. For the purpose of this study proteinuria was defined as a 24-hour urinary protein excretion rate of >/=20 and <200 microg/min. Risk factors included were smoking, blood pressure, body mass index, serum total cholesterol, hyperglycemia, and proteinuria. Subjects with stroke had higher proteinuria proportion and systolic and diastolic blood pressures. Both frequency of antihypertensive treatment and antihypertensive drugs used were similar among subjects with and without stroke. In multivariate logistic regression analysis, the ORs and 95% CIs for the variables identified as risk factors for stroke were as follows: systolic pressure (OR 3.10; 95% CI 3.01 to 4.21; P=0.03); diastolic pressure (OR 3.30; 95% CI 1.04 to 4.48; P<0.0001); fasting glucose >/=11.1 mmol (OR 1.82; 905% CI 1.4 to 3.8; P=0.04), HbA1c >/=9.5% (OR 1.7; 95% CI 1.3 to 5.1; P<0.01), and proteinuria (OR 3.23; 95% CI 1.06 to 4.36; P<0.0001). Our case-control study gives evidence that proteinuria is an independent risk factor for ischemic stroke in patients with NIDDM.

Relapsing Membranous Nephropathy

Background: Although controversial, treatment of membranous nephropathy appears to yield a reduction in the degree of proteinuria and conservation of renal function. Methods: We report herein our experience with the treatment with steroids alone (group II, n = 13), or in combination with immunosuppressants (group III, n = 19) of patients with membranous nephropathy and the nephrotic syndrome, with a mean follow-up of 8.37 years. Results: All patients underwent a first remission, with 24-hour urine protein excretion falling to 0.63 ± 0.25 g in group II and 0.62 ± 0.26 g in group III (p = NS) after 12.69 ± 10.94 months of treatment in group II and 18.95 ± 13.17 months in group III (p = NS). Three patients from group II (23%) and seven patients from group III (36.8%) experienced four and eight relapses, respectively (proteinuria in 24 h 4.0 ± 0.80 g in group II relapsers and 4.4 ± 0.87 in group III relapsers; p = NS). On treatment, all relapses remitted (second remission) after 7 ± 6.93 months of therapy for group II and 8.6 ± 6.70 months of treatment for group III (p = NS). Thereafter, no patients from group II, but 3 patients from group III (33.3%) had a second relapse. After treatment, all relapses remitted (third remission) in 3.3 ± 1.53 months of therapy. Conclusions: These studies show that relapses, which occur in one-third of patients, respond favorably to treatment albeit remitting in approximately half the time, and that the duration of remission gets progressively longer in the later compared to the earlier remission.

A Low-Calorie Unrestricted Protein Diet Attenuates Kidney Damage in Uninephrectomized Spontaneously Hypertensive Rats

Background/Aims: Uninephrectomized, spontaneously hypertensive rats (UNX-SHR) develop glomerular hyperfiltration, hyperfusion, and interstitial infiltrate of the remnant kidney. Consequently, UNX-SHR is a useful animal model to investigate mechanisms involved in the progression of hypertensive renal disease. Methods: Body weight; tail systolic blood pressure (SBP); urine excretion of protein, urea, and electrolytes; and serum biochemistry were determined in UNX-SHR at 2 months of age prior to uninephrectomy (week 0), prior to treatment (week 8) with a low-calorie (LC) or control diet, and one month after diet treatment (week 12). The LC diet was modified to allow equal intake of protein, sodium phosphorus, and other nutrients in both groups. Results: UNX-SHR treated with the LC diet had significantly lower body weights and SBP at the end of the experiment than did the controls (p < 0.0001). Changes in serum biochemistry and 24-hour urinary excretion of protein, sodium, potassium, and urea nitrogen in both groups were not statistically significant. The final glomerular filtration rate and renal plasma flow were similar in both groups, but the LC diet significantly reduced the glomerular damage index (0.0007), mesangial expansion index (p < 0.002), volume of interstitium per cortex (p < 0.0003), tubular interstitium volume fraction (p < 0.0008), glomerular volume (p < 0.02), and remnant kidney weight (p < 0.01). Conclusion: We demonstrated that in UNX-SHR, the prevention of renal damage by LC diet may involve diminished glomerular growth and interstitial infiltrate without changes in renal hemodynamics. Consequently, LC diet, regardless of protein ingestion, may be an important tool in the prevention of renal damage in hypertension. Additional studies of obese-hypertensive rats may confirm the beneficial effect of a LC diet and weight reduction on the renal damage of obesity-hypertension.

Risk factors for development of proteinuria in chronic spinal cord injury.

A retrospective, case-control study was performed to investigate the risk factors that may contribute to the development of proteinuria in patients with chronic spinal cord injury (SCI). During an 18-month period, 31 subjects with a 24-hour protein excretion of 1.0 g or greater were identified. Three control subjects with SCIs with a 24-hour urinary protein excretion of less than 1.0 g during the same time period were randomly selected for each study subject with proteinuria. Clinical data, including level and duration of injury, age, presence of indwelling bladder catheter, number of decubitus ulcer procedures, serum albumin and creatinine concentrations, hematocrit, creatinine clearance, and the presence of hypertension and diabetes mellitus, were obtained from medical records. Subjects with proteinuria had other evidence of renal dysfunction with greater serum creatinine concentrations and reduced creatinine clearances, serum albumin concentrations, and hematocrits. Proteinuric subjects were older, had a longer duration of injury, had undergone a greater number of decubitus ulcer procedures, and were more likely to have hypertension and indwelling bladder catheters. The independent predictors for the development of proteinuria using logistic stepwise multiple linear regression analysis were the use of chronic indwelling bladder catheters, number of decubitis ulcer procedures, presence of hypertension, and older age. These data suggest that inflammatory complications associated with complications of chronic SCI, rather than SCI per se, contribute to the development of proteinuria. SCI patients with proteinuria have more impaired renal function and increased mortality compared with SCI patients without proteinuria.

Hyponatremic-hypertensive syndrome with renal ischemia: an underrecognized disorder.

Renal artery stenosis or occlusion causing the hyponatremic-hypertensive syndrome has been rarely reported. Our impression, however, was that the disorder is not uncommon. Case records from patients in one city (population 350 000) presenting between 1980 and 1997 with hypertension, hyponatremia, and evidence of renal ischemia were scrutinized. Thirty-two patients fulfilling inclusion criteria were identified. Admission supine arterial pressures were high (mean 228/124 mm Hg), but there was a vigorous fall in pressure on standing (26/12.7 mm Hg recorded in 27 patients). Mean plasma concentrations of sodium (129.7 mmol/L) and potassium (2.7 mmol/L) were low, and 24-hour urine protein excretion was elevated in 19 of 26 patients. Twenty-two of the 32 patients were female, the majority were asthenic, and all but 5 were smokers. Symptoms precipitating hospitalization were headache, clouding of consciousness, confusion, weakness, weight loss, thirst, and polyuria. Plasma renin levels, measured in 20 patients, were elevated in most cases and correlated inversely (r=-0.63, P<0.01) with the plasma sodium concentration. The hyponatremic-hypertensive syndrome in patients with renal ischemia is not rare: Rather, it is underreported. It tends to affect elderly asthenic women who smoke heavily. Stimulation of renin release from the ischemic kidney is probably central to the pathophysiology. The syndrome deserves better recognition to ensure appropriate investigations and management.

Effect of valsartan on renal function in patients with hypertension and stable renal insufficiency

Angiotensin II AT 1 receptor blockers have been introduced into clinical practice; however, larger-scale information on their tolerability and effects on renal function in patients with hypertension and renal insufficiency is limited. A 6-month, double-masked, placebo-controlled, multicenter, clinical trial was performed to address this issue. Fifty-six adults with hypertension and reduced renal function were studied. They received the AT 1 receptor blocker valsartan (80 mg/d) or placebo, in addition to other antihypertensive drugs. The renal variables studied were glomerular filtration rate, effective renal plasma flow, renal blood flow, serum creatinine level, and 24-hour urinary albumin, protein, and urea excretion. Drug tolerability was also assessed. Differences were not significant between the valsartan and placebo groups with respect to effects on any renal function variable. Furthermore, the tolerability of valsartan and placebo was not different. Compared with placebo, valsartan lowered systolic and diastolic blood pressures. Data from this study suggest that valsartan is well tolerated and effective in treating patients with hypertension and reduced renal function.

Assessment of urinary endothelin-1 and nitric oxide levels and their relationship with clinical and pathologic types in primary glomerulonephritis.

To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.

Interleukin-6 Localization and the Prognosis of IgA Nephropathy

Various cytokines and growth factors may be involved in IgA nephropathy. To clarify whether interleukin-6 was a prognostic factor for this disease, we investigated interleukin-6 positivity of renal biopsy specimens and its relationship with the prognosis. The subjects were 90 patients with IgA nephropathy (42 males and 48 females with a median age of 32.7 ± 13.8 years). Renal biopsy specimens were stained for interleukin-6 using an enzyme-antibody method. Fifty-two of 90 patients showed glomerular positivity for interleukin-6. Among the patients positive for interleukin-6, 24-hour urinary protein excretion and serum creatinine levels were significantly higher at the time of biopsy than in the patients without interleukin-6 positivity, while creatinine clearance was significantly lower. In the interleukin-6-positive patients without steroid therapy, serum creatinine increased significantly after 1 year (Δs-Cr; 1.04 ± 0.45 mg/dl) and creatinine clearance decreased significantly (ΔCcr; –11.7 ± 3.2 ml/min) compared to the interleukin-6-negative patients without steroid therapy. Steroid therapy improved 24-hour urinary protein excretion, serum creatinine, and creatinine clearance in the interleukin-6-positive patients, while these parameters worsened without steroid therapy. On the other hand, the IL-6-negative patients showed no differences of clinical parameters irrespective of the presence or absence of steroid therapy. In conclusion, glomerular interleukin-6 positivity may be a prognostic factor and an indicator of the need for steroid therapy in IgA nephropathy.

Limited evaluation of microscopic hematuria in pediatrics.

The purpose was to determine the value of the standard laboratory and radiologic evaluation of microscopic hematuria in children, and to determine the prevalence of idiopathic hypercalciuria in those children referred for evaluation of unexplained microscopic hematuria. This was a retrospective study of 325 children referred from 1985 to 1994 for the evaluation of asymptomatic microscopic hematuria. The diagnostic studies reviewed included serum creatinine, blood urea nitrogen, serum electrolyte studies, serum complement concentration, antinuclear antibody, urinalysis, urine calcium to creatinine ratios, urinary protein to creatinine ratio and/or 24-hour urinary protein excretion, renal ultrasounds, intravenous pyelograms, voiding cystourethrograms, and historical information. All creatinine and electrolyte values were normal for age, and none of the biochemical tests obtained in the children with hypercalciuria was abnormal. Of the 325 patients with idiopathic microscopic hematuria, only 18 had abnormal renal ultrasound examinations and 9 voiding cystourethrograms showed low-grade reflux. Hypercalciuria was found in 29 patients. The family history was positive for urolithiasis in 16% of patients without hypercalciuria compared with 14% of patients with hypercalciuria. A positive family history of hematuria was reported in 25% of patients; 62 patients did not have hypercalciuria and 4 of the patients had hypercalciuria. Microscopic hematuria in children is a benign finding in the vast majority of children. Our data demonstrate that a renal ultrasound, voiding cystourethrogram, cystoscopy, and renal biopsy are not indicated in the work-up of microscopic hematuria, and microhematuria in the otherwise healthy child is a minimal health threat, rarely indicative of serious illness.

Salazosulfapyridine(SASP)投与が有効であった慢性間接リウマチに伴う続発性アミロイド腎症の1例

A 55-year old female with rheumatoid arthritis (RA) had presented with proteinuria since July 1996. She was referred to us for persistent edema on her face and legs in November 1996. On admission, her 24-hour urinary protein excretion was 4.4 g/day, total serum protein level was 5.3 g/dl, and serum level of amyloid A protein (SAA) was elevated to 45.8 mg/ml. A percutaneous renal biopsy was performed, and light microscopy revealed varying degrees of amyloid deposits in the mesangial areas and arteriolar walls. The diagnosis of secondary amyloidosis (AA amyloidosis) was based on immunohistochemical staining for amyloid A protein using monoclonal antibody against SAA. Four weeks after treatment with salazosulfapyridine (SASP) and dipyridamole, proteinuria began to decrease and the edema had disappeared. Finally she recovered from nephrotic syndrome. AA amyloidosis has been thought to have a poor prognosis, with progression to renal failure. Since there is no specific effective therapy for the disease, it is very important to reduce the activity of the underlying cause. In our patient with renal amyloidosis following RA, SASP was evidently effective for arthritis and improvement of renal function. SASP might have a beneficial effect on AA amyloidosis by suppressing inflammatory cytokines.

Ga-67 scintigraphy in lupus nephritis.

Lupus nephritis is a disease characterized by flareups and remissions. Evaluation of disease activity is important for therapeutic decisions and prognosis. In this study, 46 patients with lupus nephritis were evaluated by Ga-67 scintigraphy. Delayed 48-hour Ga-67 images were performed to evaluate kidney uptake. A patient with a 24-hour urinary protein excretion of 3 g or more or a serum creatinine level greater than 1.5 mg/dl was considered to have active lupus nephritis. Renal disease was active in 22 patients and inactive in 24 patients. Of the 22 patients with active renal disease, 18 (81.8%) showed positive Ga-67 results, whereas only 12.5% (3 of 24) of patients with inactive renal disease showed a positive Ga-67 study. The difference between the two groups was significant. Patients with positive Ga-67 scans had a significantly higher serum creatinine level and 24-hour urine protein value than patients with negative Ga-67 scans. In addition, all of the patients (100%) with a 24-hour urine protein greater than 4 g/day had a positive Ga-67 scan. It appears that Ga-67 scintigraphy is useful for the evaluation of disease activity in lupus nephritis.

Hemodialysis vascular access: Variable thrombus-free survival in three subpopulations of black patients

Hemodialysis vascular access-related problems account for most hospitalizations in chronic hemodialysis patients. Although some co- morbid risk factors for early fistula failures have been described, a great deal of unknown exists as to why access survival is favorable in some patients. In this longitudinal study, fistulae patency and thrombosis episodes were monitored from placement date in three groups of end-stage renal disease (ESRD) patients who have been on dialysis for > or =90 days. Thirty-six patients (29 male; 80%) with a mean age of 42+/-2 years were monitored. The groups consisted of eight patients with biopsy-confirmed focal segmental glomeruloscierosis (FSGS), 13 with acquired immunodeficiency syndrome-related nephropathy (human immunodeficiency virus [HIV]), and 15 with hypertensive ESRD (hypertensive nephrosclerosis [HTN]) who served as controls. Diabetics and patients aged > or =64 years were excluded. Twenty-five of 36 (69%) fistulae were prosthetic (AVG), while 11 (31%) were native (AVF). The FSGS group was more likely to have an AVG (87.5%), while 54% of the HIV group had an AVG. The thrombosis event rate was significantly greater among the FSGS patients (3/patient-year) than the HIV (0.15/patient- year) and HTN (0.5/patient-year) patients (P < 0.0001 and P < 0.002, respectively). The mean thrombosis-free duration for both AVG and AVF among the HIV and HTN groups were 318.5+/-17 days and 311.7+/-22.5 days, respectively. These were significantly greater than in the FSGS group (26.5+/-7 days; P < 0.0001). The cumulative 1-year patency rate for AVG among the HIV and HTN groups was 85% and 65%, respectively, while that of the FSGS group was 0%. Kaplan-Meier hazard analysis showed that all groups were at risk of access thrombosis as time progressed, but the FSGS group had the highest risk of access thrombosis, which began from the date of placement and increased exponentially with time. The increased thrombosis rate among the patients in the FSGS group correlated with their weight (R = 0.8, P = 0.003) and pre-ESRD 24-hour urinary protein excretion (R = 0.9, P = 0.001). The HIV status appeared to confer enhanced hemodialysis access survival. This may be related to the high rate of native fistulae placement and favorable vascular reactivity to shear stress. Accelerated atherosclerosis and small caliber vessels may be responsible for the poor fistulae outcome among the FSGS group. More studies will be necessary to further explore these findings. (Am J Kidney Dis 1998 Feb;31(2):250-6)