Early elimination of uremic toxin ameliorates AKI-to-CKD transition.

Acute kidney injury (AKI)-related fibrosis is emerging as a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still poorly understood. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The present study aims to elucidate the effects of IS on tubular damage and its involvement in the pathogenesis of AKI-to-CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter but not observed in the small-molecule uremic toxins of the unilateral ischemia-reperfusion injury (UIRI) without a contralateral nephrectomy model. Serum IS is positively correlated with renal fibrosis and binding immunoglobulin protein (BiP) and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI-to-CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of endoplasmic reticulum (ER) stress, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia-reperfusion (H/R) induced G2/M cell cycle arrest, epithelial-mesenchymal transition (EMT) and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-phenylbutyric acid (4-PBA), successfully reversed the above-mentioned AKI-to-CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention and/or treatment of the AKI-to-CKD transition.

An in-vitro assay using human spermatozoa to detect toxicity of biologically active substances.

Identifying the key toxic players within an in-vivo toxic syndrome is crucial to develop targeted therapies. Here, we established a novel method that characterizes the effect of single substances by means of an ex-vivo incubation set-up. We found that primary human spermatozoa elicit a distinct motile response on a (uremic) toxic milieu. Specifically, this approach describes the influence of a bulk toxic environment (uremia) as well as single substances (uremic toxins) by real-time analyzing motile cellular behavior. We established the human spermatozoa-based toxicity testing (HSTT) for detecting single substance-induced toxicity to be used as a screening tool to identify in-vivo toxins. Further, we propose an application of the HSTT as a method of clinical use to evaluate toxin-removing interventions (hemodialysis).

Systemic Sarcoidosis Presenting with Renal Involvement Caused by Various Sarcoidosis-associated Pathophysiological Conditions.

A 61-year-old man was diagnosed with sarcoidosis involving the lungs, eyes, parotid gland and extrathoracic lymph nodes complicated by chronic kidney injury and hypercalcemia. Kidney biopsy showed non-specific interstitial nephritis and nephrosclerosis. However, immunohistochemical staining of cell surface markers revealed a multinucleated giant macrophage surrounded by T-cells, suggesting granulomatous interstitial nephritis. Corticosteroid improved the kidney function, and reduced the serum levels of calcium and angiotensin-converting enzyme. Sarcoid nephropathy may be caused by the combination of several sarcoidosis-associated pathophysiological conditions and a comprehensive kidney examination should be performed to assess the type of injury when determining a treatment strategy.

Hyperuricemia as a Predictive Marker for Progression of Nephrosclerosis: Clinical Assessment of Prognostic Factors in Biopsy-Proven Arterial/Arteriolar Nephrosclerosis.

AIM: The influence of serum urate on kidney disease is attracting attention, but the effects of uric acid (UA) on nephrosclerosis have not been elucidated. METHODS: We reviewed data from 45 patients diagnosed with arterial/arteriolar nephrosclerosis. The renal outcomes of the arterial/arteriolar nephrosclerosis patients were assessed by performing logistic and Cox regression analyses. A Kaplan-Meier analysis was used to evaluate the impact of hyperuricemia (HU) on kidney survival. The renal outcomes of patients with and without HU were compared by using a propensity score-matched cohort. RESULTS: The logistic regression models showed no significant differences in renal outcomes, according to baseline parameters or follow-up parameters, except the serum UA value and body mass index (BMI). Baseline serum UA level had the highest odds ratio (OR) for estimated glomerular filtration rate (eGFR) decline (OR, 1.86; 95% confidence interval (CI), 1.12 to 3.45), among the parameters assessed. In the multivariate Cox regression analysis, HU (UA ≥8.0 mg/dL) (P=0.01) and BMI (P=0.03) were significantly associated with a ≥50% eGFR decline or ESRD. The Kaplan-Meier analysis in the propensity score-matched cohort indicated that the renal survival rate of the group of arterial/arteriolar nephrosclerosis patients with HU was significantly lower than that of the group without HU (log rank, P=0.03). CONCLUSION: The results of this study suggest that the baseline serum UA value can serve as a renal outcome predictor in arterial/arteriolar nephrosclerosis patients.

The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry.

BACKGROUND/AIMS: Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD). METHODS: Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008. RESULTS: Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31-1.81 and HR, 1.44; 95% CI, 1.13-1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79-1.65). CONCLUSIONS: Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients.

Effects of the N/L-type calcium channel blocker cilnidipine on nephropathy and uric acid metabolism in hypertensive patients with chronic kidney disease (J-CIRCLE study).

This study assessed the urinary albumin/creatinine ratio (ACR) and uric acid metabolism in 70 hypertensive patients with chronic kidney disease in whom urinary ACR had remained ≥30 mg/g under the treatment of the L-type calcium channel blocker amlodipine. Three months after switching to the N/L-type calcium channel blocker cilnidipine, blood pressure (BP) did not change; however, urinary ACR significantly decreased with cilnidipine. Serum uric acid levels showed no significant change. In cases where uric acid production had been high (urinary uric acid/creatinine ratio ≥0.5), the urinary uric acid/creatinine ratio decreased significantly after cilnidipine treatment, suggesting that cilnidipine can suppress excessive uric acid formation. These results suggest that switching from amlodipine to cilnidipine results in a significant reduction in urinary ACR as well as significant reduction in uric acid production. Thus, cilnidipine is more useful than amlodipine in improving albuminuria and uric acid metabolism in hypertensive patients with chronic kidney disease.

Serum potassium predicts time to blood pressure response among African Americans with hypertensive nephrosclerosis.

It is not known whether serum potassium levels affect blood pressure response to antihypertensive medication. The African American Study of Kidney Disease and Hypertension (AASK) Genomics Study (N=828) is a subset of the AASK trial that randomized 1094 African American men and women with hypertensive nephrosclerosis to ramipril, amlodipine or metoprolol. Participants were also randomized to a usual (102-107 mm Hg) or low (≤92 mm Hg) mean arterial pressure (MAP) treatment goal. Time-to-event analyses were used to determine the relationship between serum potassium at randomization and time (days) to reach an MAP of 107 mm Hg. Mean baseline serum potassium was 4.22 mmol l(-1) (s.d.±0.56 and range 2.8-6.0) and the median days to reach target MAP was 32 (interquartile range 8-95). The adjusted hazard ratio (HR) for each 1 mmol l(-1) increase in serum potassium was 1.31 (95% confidence interval (CI): 1.08-1.59) in the usual MAP group, and 1.21 (95% CI: 1.02-1.44) in the low MAP group. Secondary findings suggested that women in the usual MAP group on amlodipine were more likely to reach target MAP compared with women randomized to ramipril (HR: 2.05, 95% CI: 1.30-3.21). Older subjects in the low MAP group (≥55 years) were also more likely to reach target MAP on amlodipine compared with ramipril (HR: 1.57, 95% CI: 1.03-2.38). Serum potassium appears to be a significant predictor of time to blood pressure response, independent of drug class. The effect of serum potassium on blood pressure response to antihypertensive medications needs to be further studied in different patient populations.

Net endogenous acid production is associated with a faster decline in GFR in African Americans.

Increased acid excretion may promote renal injury. To evaluate this in African Americans with hypertensive nephrosclerosis, we studied the association between the net endogenous acid production and progression of kidney disease in 632 patients in the AASK trial. Protein and potassium intakes were estimated from 24 h urea nitrogen and potassium excretion, and used to estimate net endogenous acid production, averaged over 2 years, approximating routine intake. The link between net endogenous acid production and the I(125)iothalamate glomerular filtration rate (iGFR) and time to end-stage renal disease or doubling of serum creatinine was analyzed using mixed models and Cox proportional hazards regressions. The trend in higher net endogenous acid production was significantly associated with a faster decline in iGFR over a median of 3.2 years. After adjustment for age, body mass index, baseline iGFR, urine protein-to-creatinine ratio, and randomized treatment group, the trend in higher net endogenous acid production remained significantly associated with a faster decline in iGFR at a rate of 1.01 ml/min per 1.73 m(2) per year faster in the highest compared to the lowest quartile. However, in time-to-event analyses over a median of 7.7 years, the adjusted hazard ratio (1.10) for composite renal events per 25 mEq/day higher net endogenous acid production was not significant. Hence, our findings implicate endogenous acid production as a potential modifiable risk factor for progressive kidney disease.

Renal histology in patients with elevated serum creatinine and concurrent normal urinalysis.

INTRODUCTION: Diagnosis of kidney disease is currently and primarily based on the measurement of serum creatinine, blood urea nitrogen, and urine output, and most kidney diseases with elevated serum creatinine accompany abnormal findings of urinalysis with microscopy, such as proteinuria or hematuria. The purpose of the current study was to determine the histologic diagnosis of patients with elevated serum creatinine and a concurrent normal urinalysis without underlying disease. METHODS: The medical records of patients who had undergone kidney biopsies between January 1, 2003 and March 1, 2008 in three medical centers were retrospectively reviewed. The patients with an elevated serum creatinine level and a normal urinalysis were enrolled. The exclusion criteria were as follows: diabetes mellitus; hypertension; chronic liver disease; malignancies; autoimmune diseases; dependence on medications; hypokalemic nephropathy; age < 18 years. Age, duration of follow-up, post-biopsy management, and the change in levels of BUN and serum creatinine from pre-biopsy to the last visit were analyzed. RESULTS: All 15 patients were included. The most frequent single diagnosis was acute interstitial interstitial nephritis, followed by hypertensive nephrosclerosis. Chronic interstitial nephritis, mesangial proliferative glomerulonephritis, acute tubular necrosis, secondary amyoloidosis, focal segmental glomerulosclerosis, and minor glomerular change were listed. The young group (< 40 years of age) included more patients with acute interstitial nephritis, and the old group (≥ 40 years of age) included more patients with hypertensive nephrosclerosis. CONCLUSION: Based on a correct histological diagnosis, all of the patients, except one, were properly managed and had preserved kidney function until the last visit.

[Early diagnosis of nephrosclerosis in children with vesicoureteral reflux].

Comparison of results of standard complex of survey with changes of urine levels of biological inflammatory marker (MCP-1), marker of fibrogenesis (TGF-beta1), marker of angiogenesis (VEGF), markers of nephron damage (collagen IV, alpha-GST, pi-GST) in 140 children with vesicoureteral reflux before and 6 months after treatment was performed. It was found that nephrosclerotic process occurs even at low degrees of vesicoureteral reflux. Even in the absence of structural and functional disorders of the kidneys according to traditional methods of evaluation, there were significant changes in the levels of biological markers of inflammation, fibrosis, and angiogenesis, as well as damage of main elements of the nephron. The method for calculating the "index of early renal damage" is proposed; method allows to monitor the state of the renal parenchyma of children with this disease.

"Benign" hypertensive nephrosclerosis.

BACKGROUND: Whether benign hypertensive nephrosclerosis (BHN) causes end-stage renal failure (ESRF) is controversial. One reason for this is the lack of biopsy evidence confirming the clinical diagnosis in most cases. AIM: To investigate whether biopsy-proven BHN leads to ESRF. DESIGN: Retrospective analysis. METHODS: We analysed all cases of biopsy-proven BHN from a single centre over a period of 20 years (n = 60), followed-up for a mean +/- SD 6.7 +/- 5.5 years. RESULTS: Patients were divided into those with stable renal function (n = 17) and those with declining function (n = 43). Mean eGFR at the time of biopsy was lower in the declining function group (29 +/- 3 vs. 44 +/- 4 ml/min/1.73 m(2), serum creatinine 280 +/- 165 vs. 161 +/- 89 mumol/l, p < 0.001), of whom 72% progressed to ESRF. Median renal survival for the whole group was 6.8 years, with 5- and 10-year survivals of 56% and 35%, respectively. Renal survival was significantly affected by initial serum creatinine, and mean systolic and diastolic blood pressures during follow-up period. Mean protein excretion was higher in the declining group, but not significantly so. On multivariate analysis, only diastolic blood pressure during follow-up predicted renal survival (p = 0.017). Median patient survival for the whole group was 9.95 years post renal biopsy, with 5- and 10-year survivals of 70% and 49% respectively. Survival was affected by initial serum creatinine, initial serum albumin and mean systolic blood pressure during follow-up. On multivariate analysis, only initial serum creatinine was significantly correlated with survival (p = 0.017). DISCUSSION: Biopsy-proven BHN led to ESRF in a high percentage of our patients, and was associated with significant mortality.

Effects of valsartan on the progression of chronic renal insufficiency in patients with nondiabetic renal diseases.

The present study tested the effects of valsartan, an angiotensin II receptor blocker, on the progression of renal insufficiency in patients with nondiabetic renal diseases. The study subjects were 22 patients with nondiabetic renal diseases whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dl. Valsartan (40-80 mg) or placebo was given once daily for 1 year each in a random crossover manner. In both periods, antihypertensive medications were titrated when the blood pressure was not lower than 140/90 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study periods. The average blood pressure was comparable between the valsartan and the placebo periods (130 +/- 9/86 +/- 6 vs. 131 +/- 8/86 +/- 6 mmHg). Serum Cr significantly increased from 1.9 +/- 0.5 to 2.3 +/- 0.8 mg/dl (p < 0.001) during the placebo period, but the change was insignificant in the valsartan period (2.1 +/- 0.6 to 2.2 +/- 0.9 mg/dl). The slope of decrease in the reciprocal of serum Cr was steeper in the placebo period than in the valsartan period (-0.064 +/- 0.070/year vs. -0.005 +/- 0.050/year, p < 0.01). During the valsartan period, urinary protein excretion was less than that during the placebo period (0.75 +/- 0.73 vs. 1.24 +/- 0.92 g/g Cr, p < 0.001). Serum K was significantly higher in the valsartan period than in the placebo period (4.6 +/- 0.5 vs. 4.4 +/- 0.5 mEq/l, p < 0.05); however, no patients discontinued taking valsartan as a result of hyperkalemia. It is possible that long-term treatment with an angiotensin II receptor blocker, valsartan, is effective at retarding the deterioration of renal function in patients with nondiabetic renal disease by a mechanism independent of blood pressure reduction.

Osteocalcin and myoglobin removal in on-line hemodiafiltration versus low- and high-flux hemodialysis.

BACKGROUND: Removal of medium and large solutes is poor with low-flux (LF-HD) and limited with high-flux hemodialysis (HF-HD) and on-line hemodiafiltration (OL-HDF). In clinical practice, there are few in vivo solute markers. Osteocalcin is a protein with a molecular mass of 5,800 daltons, and myoglobin is a large molecule with a molecular mass of 17,200 daltons. The aim of this study was to evaluate the impact of OL-HDF on in vivo removal of a wide spectrum of solutes (urea, creatinine, osteocalcin, beta2-microglobulin, and myoglobin) in comparison to LF-HD and HF-HD. METHODS: Twenty-three patients (15 men, 8 women) were studied. Every patient underwent three dialysis sessions with routine HD parameters. We compared 1.8-m2 polysulfone LF-HD and 1.8-m2 polysulfone HF-HD versus OL-HDF. Predialysis and postdialysis solute concentrations were measured. The percentage of reduction ratio for each solute was calculated. RESULTS: Mean values for predialysis osteocalcin, beta2-microglobulin, and myoglobin were 16.3 +/- 21 ng/mL, 27.4 +/- 5 mg/L, and 239 +/- 162 ng/mL in LF-HD, respectively. Urea and creatinine reduction ratios were similar in LF-HD and HF-HD and only 1.2% higher in OL-HDF. Osteocalcin, beta2-microglobulin, and myoglobin reduction ratios for LF-HD were negligible. Mean osteocalcin reduction rates were 54.2% +/- 12% for HF-HD versus 63.5% +/- 9% for OL-HDF (reinfusion volume, 26.8 +/- 5 L/session; P < 0.01). Mean beta2-microglobulin reduction rates were 60.1% +/- 9% for HF-HD versus 75.4% +/- 9% for OL-HDF (P < 0.01). Mean myoglobin reduction rates were 24.5% +/- 6% and 62.7% +/- 9% for HF-HD and OL-HDF, respectively (P < 0.01). CONCLUSION: LF-HD does not seem to remove solutes with a molecular weight greater than 5,800 daltons. OL-HDF provides marked enhancement of convection volume and enables a significant increase in osteocalcin and beta2-microglobulin removal. Myoglobin extraction is nil with LF-HD, very low with HF-HD, and only adequate with OL-HDF.

Increased fibrinogen levels and hemostatic abnormalities in patients with arteriolar nephrosclerosis: association with cardiovascular events.

Increased plasma fibrinogen levels and hemostatic abnormalities suggestive of a prothrombotic state are present in patients with end-stage renal failure and could contribute to increased cardiovascular morbidity in these patients. We investigated the relationship between abnormalities of the hemostatic system and the degree of renal failure and whether these abnormalities are associated with increased prevalence of cardiovascular events in patients with arteriolar nephrosclerosis. In 425 patients recruited at a hypertension clinic we assessed the renal function by creatinine clearance, urinary protein excretion, and microalbuminuria, the prevalence of atherosclerotic disease, and measured prothrombin time, activated partial thromboplastin time. fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, and antithrombin. Early impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) caused by arteriolar nephrosclerosis was found in 172 patients. Patients with early renal failure were significantly older and had significantly greater values of blood pressure, plasma fibrinogen, F1+2, and D-dimer than patients with normal renal function. Elevated D-dimer and fibrinogen levels were independently associated with the presence of decreased creatinine clearance. Log fibrinogen, log F1+2, and log D-dimer were inversely correlated with creatinine clearance. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was significantly greater in patients with mild renal failure than in those with normal renal function. Elevated levels of fibrinogen and D-dimer were associated with the presence of atherosclerotic disease independent of renal function and other risk factors. In conclusion, changes in hemostatic parameters occur early in the course of renal failure in patients with arteriolar nephrosclerosis, suggesting a prothrombotic state that may contribute to the risk for atherosclerotic disease at all levels of renal function.

[Hormonal disorders in patients with chronic pyelonephritis with nephrosclerosis and kidney failure]. / Gormonal'nye narusheniia u bol'nykh khronicheskim pielonefritom s nefrosklerozom i pochechnoi nedostatochnost'iu.

Blood plasma content was studied of hydrocortisone, parathyroid hormone (PTH) and calcitonin in patients with chronic pyelonephritis (ChP) using methods of radioimmunologic and immunoenzymatic analyses. ChP patients had marked alterations of blood plasma levels of hydrocortisone, PTH and calcytonin, with the reduced levels of hydrocortisone and hypercalcitoninamia being noted during the early stages of nephrosclerosis. It is suggested that hydrocortisone and calcitonin content in blood of ChP patients might be used as indicators of state of the endocrine mechanisms controlling the renal connective tissue metabolism during the early stages of nephrosclerosis. The above measure will also be helpful in the assessment of activity of the sclerotic process in the kidneys, prognosis of the outcome of the medical condition, and development of treatment options of adequate pathogenetic therapy.

Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis: results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Measurement of GFR is considered the standard for estimating renal function. However, standardized accurate GFR methodology is expensive and cumbersome; therefore, estimates of GFR based on serum creatinine concentration have been employed. The purpose of the study presented here was to assess the accuracy and precision of using serum creatinine measurements to estimate GFR in the screen cohort of The African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. GFR was estimated by four methods: 100/serum creatinine, Cockcroft-Gault equation, creatinine clearance from 24-h urine collection, and a new regression equation derived from the pilot study data. These methods were compared with renal clearance of 125I-iothalamate GFR (GFR1) in 193 hypertensive (diastolic blood pressure > or = 95 mm Hg) African-American screen (142 men, 51 women). A second GFR (GFR2) was performed in 98 screen who were eligible (GFR1 25-70 mL/min per 1.73 m2) for the pilot study. Accuracy was assessed by the difference of 125I-iothalamate GFR-estimated GFR (delta GFR), and precision was estimated from the combined root mean squared error (CRMSE) and the coefficient of determination (r2). The results for accuracy (+/- SD) and precision were as follows: (1) 100/Scr, delta GFR = -0.76 +/- 16.5, CRMSE = 16.5, r2 = 0.69; (2) Cockcroft-Gault, delta GFR = 9.56 +/- 14.9, CRMSE = 17.7, r2 = 0.66; 3) 24-h creatinine clearance, delta GFR = 0.79 +/- 20.7, CRMSE = 20.7, r2 = 0.49; 4) New equation delta GFR = -0.08 +/- 12.8, CRMSE 12.7, r2 = 0.75. In comparison, a second GFR (GFR2, N = 98) had delta GFR = 1.36 +/- 8.48, CRMSE 8.6, r2 = 0.75. Estimates based on 100/SCr and the new equation were the most precise. It was concluded that GFR estimated by serum creatinine is superior to outpatient 24-h urine creatinine clearance in this population. Serum creatinine values can be used to provide a reasonably accurate estimate of GFR in hypertensive African Americans.

[Hydrocortisol, parathyroid hormone and calcitonin in blood of patients with chronic pyelonephritis and nephrosclesosis]. / Soderzhanie kortizola, paratiroidnogo gormona i kal'tsitonina v krovi bol'nykh khronicheskim pielonefritom pri razvitii nefroskleroza.

Hydrocortisole, parathyroid hormone (PTH), and calcitonin were radioimmunoassayed in the blood of patients with chronic pyelonephritis. Hydrocortisone content decreased at the early stages of nephrosclerosis before renal failure, and hypercalcitoninemia was developing. In chronic renal insufficiency hydrocortisone level normalized, hypercalcitoninemia augmented, and PTH level in the blood plasma increased. Disorders of these substances metabolism are believed to be one factor in the pathogenesis of pyelonephritic nephrosclerosis. Measurements of blood hydrocortisone and calcitonin in patients with chronic pyelonephritis can be used for early diagnosis of nephrosclerosis before its clinical manifestation as chronic pyelonephritis. Such measurements will help objectively assess the activity of the sclerotic process, timely begin proper treatment, and predict the disease course and outcome.

[Clinical study on zhengan xifeng decoction in preventing and treating hypertensive nephropathy].

Seventeen cases of hypertensive nephropathy with azotemia (test group) treated with Zhengan Xifeng Decoction (ZGXFI) and routine regimen of Western Medicine were observed. The result was compared with that of 15 cases treated with routine regimen alone (control group). After 3 months of treatment, the blood pressure, sodium excretion, blood urea nitrogen and creatinine were all reduced, while creatinine clearance rate (CCr) and residual renal function index (RRFI) were improved significantly in both groups. Compared with control group, the treatment on test group showed a more prominent effect on lowering of diastolic blood pressure, elevating the hemoglobin, reducing the blood level of triglyceride and creatinine as well as improving on CCr and RRFI, suggesting the deterioration of residual renal function could be restrained by ZGXFD, through improve the disorder of lipid metabolism, osmolality gradient and creatinine kinetics.

Possible relationship between hyperinsulinemia and glomerular hypertrophy in nephrosclerosis.

Hyperinsulinemia is potentially associated with the development of vascular sclerosis. On the other hand, the relationship between hyperinsulinemia and nephrosclerosis has not been elucidated. In this investigation clinicopathological studies were performed in 40 patients with nephrosclerosis, with special attention to the relationship between hyperinsulinemia and glomerular hypertrophy. Forty patients with biopsy-proven nephrosclerosis were divided into two groups by the 75-g oral glucose tolerance test (OGTT): group A, 2-hr plasma glucose concentration > 140 mg/dL (n = 25); group B, 140 < or = 2-hr plasma glucose < 200 mg/dL (n = 15). Patients with diabetes mellitus or diabetic nephropathy were not included. Morphometric analysis of the glomeruli revealed a significantly larger mean glomerular volume in subjects with nephrosclerosis in both subgroups. In addition, the mean glomerular volume was significantly correlated with the fasting insulin level, while no significant correlation was observed between the mean glomerular volume and creatinine clearance or degree of global sclerosis. These results indicate that hyperinsulinemia may be intimately related to glomerular hypertrophy in patients with nephrosclerosis.