Renin-producing renal cell carcinomas—clinical and experimental investigations on a special form of renal hypertension

Summary The pathogenetic relationship between tumour and hypertension was investigated in 129 patients with renal cell carcinoma, of whom 41 (31.8%) were hypertensive. Of these 41 patients with renal tumours and hypertension, 6 (14.6%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumour kidney to contralateral kidney ratio of between 4 and 7, and 2 patients also had secondary hyperaldosteronism. In the same 6 cases the renin content in the renal tumour tissue was significantly higher than that in tissue from the adjacent tumour-free renal cortex of the ipsilateral kidney. Immunohistochemical demonstration of renin in the tumour was only possible in these 6 cases. In 5 of these patients blood pressure returned to normal following nephrectomy; in the 6th case there was a drop in blood pressure after nephrectomy. In 3 renin-positive tumours examined, autonomous renin production was demonstrated in cell culture. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumour.     

当归或三七对兔甘油致急性肾衰的保护作用及其机制研究

目的：用甘油复制兔急性肾小管坏死(ATN)模型，观察当归、三七对ATN的保护作用，并初步探讨其机制。方法：40只健康新西兰白色家兔，等分为四组：当归组、三七组、对照组、正常组。当归、三七、对照三组均用50％甘油等渗盐水15ml/kg注入兔双后肤皮下，复制ATN模型，当归组于注射甘油后即刻，第3小时，第6小时，肌注当归注射液50mg／kg，三七组于相同时点肌注三七皂甙50mg／kg，正常组则于兔双后肢皮下注射生理盐水15ml/kg，并于相同时点注射5％葡萄糖注射液。于实验第24小时取血液、尿液和肾脏，检测血清尿素氮、肌酐、尿液总渗透压、尿总氨基酸、肾组织MDA、SOD、GSH—PX、ATP酶、Ca2^ 、肾组织病理形态学检查。结果：各组与正常组比，肌酐、尿素氮明显升高，说明模型复制成功。当归、三七纪元l例死亡，对照组死士率为30％，血清肌酐、尿素氮、丙二醛、尿总氨基酸、滤过钠排泄分数和肾组织钙含量均明显低于对照组(P＜0．01)，而肾组织ATP酶、SOD、GSH-PX活性均高于对照组(P＜0.01)，病理形态学变化轻于对照组。以上指标，当归与三七组无显著差异(P＞0．05)。结论：当归、三七对甘油所致的ATN有明显保护作用，二者效果无差异，其机制可能与二者均有改善微循环、血液流变学、抑制脂质过氧化反应、保护肾脏抗氧化酶和ATP酶活性及减轻肾组织钙超载有关。     

控制肾血管的肾脏重建治疗重度肾外伤(附15例报告)

目的：提高肾外伤手术治疗的肾单位保存率。方法：采用早期控制肾血管，必要时阻断肾血管重建伤肾的方法，治疗重度肾外伤l5例。结果：5例行肾修补术，4例行肾部分切除术，2例行肾静脉修补术，4例行肾切除术，肾切除率26．3％。结论：控制肾血管的肾脏重建术能有效减少肾脏切除率，是手术治疗肾外伤的理想方法。     

Enhanced in vivo cytotoxicity of recombinant human tumor necrosis factor with etoposide in human renal cell carcinoma

Summary The combination of tumor necrosis factor (TNF) and etoposide (ETP) was evaluated for potential cytotoxic efficacy against a human renal cell carcinoma xenograft using an in vivo assay employing an athymic mouse host with tumor implanted a the subrenal capsule site. Both antitumor efficacy (relative survival or RTS) and toxicity (weight loss) of TNF and ETP alone and in combination were evaluated. While TNF and ETP alone were mildly inhibitory (RTS 90% and 71%, respectively), the combination caused marked tumor inhibition (45% of controls). Host toxicity encountered with the combination did not exceed the toxicity associated with ETP alone, suggesting that the therapeutic index may have been augmented. It is concluded that enhanced antitumor activity without substantial augmentation of toxicity is observed with this combination, providing a rationale for further evaluation of tumor necrosis factor-based regimens for the treatment of advanced renal carcinoma.Supported by a Merit Review grant, VA Medical Research Service, Durham, NC 27710, USA     

Acute renal failure due to xanthine stones

A 9-month-old child with the skeletal abnormalities of Fuhrmann's syndrome presented with acute renal failure secondary to bilateral renal calculi. Hereditary xanthinuria was shown to be the underlying metabolic defect. Treatment with allopurinol was unsuccessful at reducing the xanthine excretion.     

Renal vein renin analysis: Limitations of its use in predicting benefit from percutaneous angioplasty

Two hundred forty-four consecutive patients (mean age 61 years), including 123 who had technically valid renal vein renin (RVR) analysis and 121 without RVR data, underwent technically successful percutaneous renal artery angioplasty (PTRA). They were retrospectively examined to evaluate the utility of RVR analysis in identifying renal hypertension (RVH), predicting benefit from PTRA, and determining if the lack of knowledge of renin levels significantly affected clinical outcome after PTRA. Abnormal RVR values were associated with clinical benefit after PTRA in 62 of 93 patients (67% sensitivity, 20% specificity, 72% positive predictive value). Clinical improvement following PTRA occurred in 31 of 37 patients with normal pre-PTRA RVR values (16% negative predictive value). RVR analysis correctly identified 86 of 117 patients with renovascular hypertension (74% sensitivity, 16% negative predictive value). Improved blood pressure (BP) control occurred in 72% with abnormal RVR analysis and 66% of the 121 patients without RVR data (p>0.1). We conclude that the very low negative predictive value significantly limited the use of RVR analysis in this elderly (mean age 60 years) patient population with a high incidence of mild renal functional impairment (mean serum creatinine 1.4 mg/dl) and bilateral renal artery stenosis (38%). The lack of pre-PTRA renin data did not significantly affect clinical outcome. If RVR data were relied upon as the exclusive selection criterion in patients of this type, many would be prevented from having the benefit of cure or improvement by PTRA.     

Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.     

Effects of Right Ventricular Failure on Renal Function During Pneumatic Left Ventricular Assist

Abstract: In an experimental dog model of acute biventricular failure, the effects of left ventricular (LV) assist on renal hemodynamics and function were evaluated. After the induction of severe cardiac failure by multiple ligation of the coronary arteries, LV assist with a 40 ml pneumatic pulsatile pump was initiated, and the aortic flow was maintained at control values. The right atrial pressure (RAP) rose to 21.3 mm Hg with the appearance of profound right ventricular (RV) failure. Renal arterial blood flow (RAF) decreased to about 60% of the control value after 2 h of LV assist. The urine volume decreased and renal function deteriorated progressively. RV assist decreased the RAP to 4.8 mm Hg, and the reduced RAF recovered. After 3 h of RV assist, the RAF returned to initial values and the urine volume increased, but renal function did not recover. Advanced biventricular failure with elevated RAP during LV assist reduced renal perfusion and impaired renal function and may be an indication for early RV assist