Thyroid hormone, but not parathyroid hormone, partially restores glucocorticoid-induced growth retardation

Growth retardation is a serious side effect of long-term glucocorticoid (GC) treatment. In order to prevent or diminish this deleterious effect, a combination therapy including growth hormone (GH), a stimulator of bone growth, is often recommended. Parathyroid hormone (PTH) and thyroid hormone (T₄) are important hormonal regulators of bone growth, and might also be helpful anabolic agents for counteracting the negative effects of GCs. Therefore, we studied the interaction of GCs in combination with a single dose of either PTH or T₄ on GC-induced growth retardation. Dexamethasone (Dex) treatment of mice for four weeks induced a significant growth inhibition of body length and weight and weights of several organs. PTH or T₄ alone did not affect the normal growth pattern. However, T₄ could partially restore the Dex-induced growth inhibition, whereas PTH could not. Although PTH did not affect total body growth, it did affect the height of the proliferative zone, which could be counteracted by Dex. This contrasts with T₄ treatment alone or in combination with Dex, which both resulted in a disturbed morphology of the growth plate. IGF-I mRNA, one of the mediators of longitudinal bone growth, was present in proliferative and hypertrophic chondrocytes. However, its expression was not affected by any of the treatments. In conclusion, T₄ but not PTH can partially counteract the effects of Dex on general body growth, with possible implications for future treatments of GC-induced growth retardation. Additionally, both T₄ and PTH, alone or in combination with Dex, have differential effects on the morphology of the growth plate.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany     

Erythrocyte susceptibility to oxidative stress in chronic renal failure patients under different substitutive treatments

An increased oxidative stress is now considered one of the major risk factors in chronic renal failure (CRF) patients that may be exacerbated by dialysis. It has been postulated that this increased oxidative stress might cause an augmented red blood cell (RBC) membrane lipid peroxidation with the consequent alteration in membrane deformability. The aim of this study was to evaluate RBC susceptibility to an in vitro induced oxidative stress and RBC antioxidant potential in different groups of CRF patients undergoing different substitutive treatment modalities. Fifteen end-stage CRF patients were evaluated in conservative treatment, 23 hemodialysis (HD) patients, 15 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 kidney transplanted patients, and 16 controls. Their RBCs were incubated with the oxidative stress-inducing agent tert-butylhydroperoxide both in the presence and in the absence of the catalase inhibitor sodium azide, and the level of malondialdehyde (MDA) (a product of lipid peroxidation), was measured at 0, 5, 10, 15, and 30 min of incubation. In addition, the RBC content of reduced glutathione (GSH) was measured by HPLC. As opposed to the controls, RBCs from end-stage CRF patients exhibited an increased sensitivity to oxidative stress induced in vitro, both in the absence and presence of a catalase inhibitor, as demonstrated by a significantly higher level of MDA production at all the incubation times (P < 0.05). Different substitutive treatments had different impacts on this phenomenon; CAPD and kidney transplantation were able to normalize this alteration while HD was not. GSH appeared to be related to the increase in RBC susceptibility to oxidative stress; its content being significantly elevated in end-stage CRF and HD patients as compared with CAPD and transplanted patients and controls (P < 0.05). No significant changes were observed in the RBC glutathione content during the HD session. The increase of GSH in RBCs of end-stage CRF and HD patients seems to indicate the existence of an adaptive mechanism under increased oxidative stress occurring in vivo. Unlike HD, the beneficial effect of CAPD on the anemia of dialysis patients might partly be due to a condition of lower oxidative stress that might in addition counterbalance the cardiovascular negative effects of dislipidemia of CAPD patients.     

Renal variant of Anderson-Fabry disease and bilateral renal cell carcinoma

Anderson-Fabry disease (AFd) is an X-linked metabolic disease with clinical manifestations secondary to accumulation of glycosphingolipids in various tissues. We report the first case in which a patient with renal variant of AFd and chronic renal failure developed bilateral conventional renal cell carcinoma. His metabolic disorder was diagnosed only after histopathologic study of the kidney specimen resected because of the tumoral lesion. There is no clear etiologic relation between the metabolic and neoplastic disease. As AFd is not common or well known and its clinical manifestations tend to be nonspecific, the disorder is often unrecognized, misdiagnosed, or diagnosed late in life. The pathologist should be aware of this disorder when evaluating a kidney specimen from patients with chronic renal failure of unknown cause.     

Changes in distribution of mercury and selenium in soluble fractions of rabbit tissues after simultaneous administration

The existing states of mercury and selenium in the blood and in soluble fractions of perfused rabbit liver and kidney were studied by gel filtration on Sephadex G-200 1 hr or 24 hr after intravenous injection of mercuric chloride and/or sodium selenite. Both mercury and selenium in the plasma and stroma-free hemolysate were found to exist in the high-molecular weight fraction following simultaneous injection of mercuric chloride and sodium selenite. Patterns in gel filtration of the plasma and the stroma-free hemolysate did not show any significant change between 1 hr and 24 hr after the administration. A similar tendency as described above was obtained with the liver-soluble fraction at 24 hr after injection of mercuric chloride and sodium selenite. A possible role of the high-molecular weight complex, which is quickly formed by the interaction of mercury and selenium in blood stream, in decreasing the acute renal toxicity of inorganic mercury is discussed.     

The effect of two different renal preservation methods on canine renal allograft survival

Summary Preservation of human cadaver kidneys for transplantation has been achieved primarily by two methods, hypothermic pulsatile perfusion with cryoprecipitated plasma and cold storage with an electrolyte solution. It has been suggested that pulsatile perfusion results in an increased antigenicity of the transplanted kidney. To investigate the possibility that pulsatile perfusion causes changes which may accelerate allograft rejection, machine preservation was compared with simple cold storage. The kidneys were preserved by either one of the two methods for 6 or 24 hours followed by allotransplantation in nephrectomised dogs. No immunosuppressive drugs were given.Kidneys which were allografted without undergoing any preservation (0 hrs) had a mean survival time of 10.4±1.7 days (n=5). Kidneys preserved by machine perfusion for 6 and 24 hours survived for 9.6±1.4 (n=5) and 10.9±1.3 (n=9) days respectively. The mean suryival time for simple cold storage for 6 and 24 hours was 9.3±1.3 (n=7) and 12.0±1.9 (n=6) days. Our findings suggest that in kidneys exposed to minimal warm ischaemia there is no significant difference between the two methods of preservation on renal allograft survival for the time intervals tested.     

Distribution of gentamicin by immunofluorescence in the guinea pig inner ear

Summary We studied the distribution of gentamicin in the inner ear, brain and kidney of the guinea pig following intraperitoneal administration or perfusion of gentamicin through the perilymphatic space. The resulting histopathologcial changes were examined by immunofluorescence using antigentamicin antiserum. After perfusion of gentamicin through the perilymphatic space, specific fluorescence was found in the cochlea, and was especially prominent in the outer hair cells, basilar membrane and basilar crest. Although no fluorescence was observed in the cochlea following intraperitoneal administration of high doses of gentamicin, type I hair cells in the vestibule were seen to be selectively stained with the antibody. Furthermore, some of the vestibular ganglion cells, Purkinje cells and unidentified nuclei in the brain stem were also stained. In particular, fine granules showing relatively intense fluorescence were recognized in the cytoplasm of the stained cells. In the cortex of kidney, only proximal tubular cells were stained with intense fluorescence. Our results suggest that the aminoglycoside antibiotics have two sites of action: one is the cell membrane of the sensory hair cells and the other is the cytoplasm.This study was supported in part by a grant from the Ministry of Education, Science and Culture of Japan, and by a Research Grant for Specific Diseases from the Ministry of Health and Welfare to the Acute Profound Deafness Research Committee of Japan     

Mechanisms of actions of guanylin peptides in the kidney

After a salty meal, stimulation of salt excretion via the kidney is a possible mechanism to prevent hypernatremia and hypervolemia. Besides the well known hormonal regulators of salt and water excretion in the distal nephron, arginine vasopressin and aldosterone, guanylin (GN) peptides produced in the intestine were proposed to be intestinal natriuretic peptides. These peptides inhibit Na⁺ absorption in the intestine and induce natriuresis, kaliuresis and diuresis in the kidney. The signaling pathway of GN peptides in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C) and increase the cellular concentration of cGMP which leads to secretion of Cl^–, HCO₃^– and water into the intestinal lumen and to inhibition of Na⁺ absorption. Guanylin peptides are filtered in the glomerulus, and additionally synthesized and excreted by tubular cells. They activate receptors located in the luminal membrane of the tubular cells along the nephron. In GC-C deficient mice renal effects of GN peptides are retained. In human, rat, and opossum proximal tubule cells, a cGMP-dependent signaling was demonstrated, but in addition GN peptides apparently also activate a PT-sensitive G-protein coupled receptor. A similar dual signaling pathway is also known for other natriuretic peptides like atrial natriuretic peptide. A cGMP-independent signaling pathway of GN peptides is also shown for principal cells of the human cortical collecting duct where the final hormonal regulation of electrolyte homeostasis takes place. This review will focus on the current knowledge on renal actions of GN peptides and specifically address novel GC-C- and cGMP-independent signaling mechanisms.     

Single-session percutaneous ethanol sclerotherapy in simple renal cysts in children: long-term follow-up

Background: Simple renal cysts are rare in children and managed conservatively unless symptomatic. Objective: To demonstrate the efficacy and long-term results of single-session ethanol sclerotherapy in symptomatic simple renal cysts in children. Materials and methods: Three simple renal cysts in three children (age 1, 5 and 16 years) were included in the study. Indications for treatment were flank pain (n=1), hypertension (n=1), and increasing cyst size and urinary tract infection (n=1). The mean follow-up period was 5.5 years (range 3–7 years). The procedures were performed with the guidance of US and fluoroscopy and under IV sedation. After the cystogram, 95% ethanol with a volume of 40% of the cyst volume (but not more than 100 ml) was used as the sclerosing agent. Results: Two cysts disappeared completely, while the volume reduction was 99% for the third cyst at the end of the first year. CT demonstrated calcification of the cyst without an enhancing soft-tissue component in the third one 7 years after sclerotherapy. After the procedures, hypertension and pain resolved without any medication. There were no complications during the procedures or during follow-up. Cytological examination was unremarkable in all patients. Conclusions: Percutaneous treatment of symptomatic simple renal cysts in children with single-session ethanol sclerotherapy is a safe, effective and minimally invasive procedure. Calcification owing to sclerotherapy can be observed on follow-up.     

Preoperative evaluation of live renal donors using multislice CT angiography

AIM: To determine the accuracy of multidetector row CT renal angiography in the preoperative evaluation of live kidney donors, and to identify potential pitfalls when reporting. METHODS: Between July 1998 and June 2003, 74 consecutive live renal donors underwent contrast-enhanced multidetector row CT renal angiography before donor nephrectomy. The operative notes and radiological reports of all cases were reviewed retrospectively. Where a significant discrepancy was identified, the archived images were reviewed by two radiologists in the light of the intraoperative findings. RESULTS: A total of 12 discrepancies were identified in 11 of the 74 cases (15%). In the preoperative CT angiography reports, 4 accessory arteries, 6 early-branching renal arteries, 1 duplicated renal vein and 1 accessory ureter were not identified; 9 of these were evident on review, but were not detected at the time of reporting. In 3 cases (1 accessory artery, the duplicated renal vein and the accessory ureter), the anomaly was not visible on review of the CT angiographic data, even with the benefit of hindsight. Surgical feedback during the study period resulted in modifications to CT technique and improved performance. CONCLUSION: In the majority of cases, there was good correlation between preoperative CT renal angiography and operative findings. Most discrepancies were due either to an oversight by the reporting radiologist, or failure to fully appreciate the potential surgical significance of certain findings. Regular surgical feedback plays a valuable role in improving reporting accuracy and maintaining imaging standards.     

91所医院1990～2002年小儿慢性肾衰竭1268例调查报告

目的　调查我国 1990年 1月～ 2 0 0 2年 12月间 0～ 14岁住院小儿中慢性肾衰竭 (CRF)病例的年龄、病因、临床病理特点、治疗情况及转归。方法　由中华医学会儿科学分会肾脏病学组统一组织领导 ,全国 4个直辖市、13个省及 2个自治区共 91所医院参加调查。CRF诊断以内生肌酐清除率 (CCr) <5 0ml/(min·1 73m2 )为标准。采用填写调查表形式 ,对诊断为慢性肾衰竭的住院患儿进行回顾性病例登记 ,进行相关资料统一汇总、分析。结果　 1990年 1月～ 2 0 0 2年 12月间 ,91所医院0～ 14岁住院小儿中共诊断CRF 16 5 8例 ,每年在住院的泌尿系统疾病患儿中所占比例为 0 72 %～1 75 % ,平均 1 31% ,呈逐渐上升趋势。 1997～ 2 0 0 2年与 1990～ 1996年比较 ,CRF平均年诊断例数和占泌尿系统疾病的百分数均显著增加 (P <0 0 0 1)。 12 6 8例完整资料分析显示 :男女比例 1 4 9∶1,平均发病年龄 8 2岁 ,平均确诊前病程 2 5年。主要原发病为慢性肾炎和肾病综合征 ,占 5 2 7% ,先天 /遗传性疾病约 1/4,以肾发育异常和肾囊性病为主。确诊时主要临床表现为贫血、胃肠反应、水肿、高血压和体格发育落后 ;平均血清肌酐 (SCr) 5 94 7μmol/L ,BUN 39 1mmol/L ,肾功能分级≥Ⅳ级者占 80 % ;1/3有肾萎缩 ,部分见囊性病变。多