The relationship between estimated glomerular filtration rate, demographic and anthropometric variables is mediated by muscle mass in non-diabetic patients with chronic kidney disease.

BACKGROUND: In this study (the first of two related papers), we report whether the relationship between the demographic and anthropometric variables (DA, i.e. age, gender, height and weight) employed in current creatinin (Cr)-based glomerular filtration rate (GFR) estimation equations and actual GFR is mediated by muscle mass. METHODS: We studied 77 patients (mean age +/- SD, 65.1 +/- 11.9 years) with chronic kidney disease (mean GFR 45.7 +/- 28.6 ml/min/1.73 m2). Actual GFR was measured by the renal clearance of inulin (GFR(inu)). Appendicular lean mass (ALM) and its index (ALMI) by dual energy X-ray absorptiometry provided markers of muscle mass. Multiple regression analyses identified variables explaining variance in (i) GFR, (ii) ALM and (iii) Cr. RESULTS: (i) The DA variables used in the abbreviated modification of diet in renal disease (MDRD) equation accounted for only 59.6% (P < 0.001) of the variance in GFR(inu), whilst adding ALMI explained an additional 10.4% variance (P < 0.001). If ALMI was entered first, the relationship between DA variables and GFR(inu) was reduced (for weight) or completely abolished (for age, gender and height). (ii) After inputting all the commonly used DA variables, 17.2% of the variance in ALM was unexplained. (iii) All the DA variables explained only 60.6% (P < 0.001) of the variance in Cr, whilst adding ALM explained an additional 4.2% variance (P < 0.005). CONCLUSIONS: Muscle mass explained more variance in GFR(inu) than MDRD DA variables and mediated the relationship between GFR(inu) and DA variables. Furthermore, DA variables failed to account for individual differences in muscle mass or Cr. Consequently, there is a need to validate simpler, clinically obtainable measures of muscle mass and determine whether these measures will improve GFR estimation.     

恙虫病致急性上消化道大出血、多器官功能衰竭经动脉栓塞止血抢救成功一例及文献复习

目的提升对恙虫病(TD)所致上消化道大出血(UGB)、多器官功能衰竭综合征(MOFS)和多器官功能损伤(MOD)的认知。方法分析1例58岁TD男性患者并发UGB、MOFS和MOD的救治经过。结果患者以“发热4 d,皮疹2 d”入院,发病前有野外游玩史,左侧小腿可见1个1.5 cm×1.5 cm焦痂,周围火山口样脱屑,左侧腹股沟淋巴结肿大。实验室检查提示丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Scr)、降钙素原(PCT)、羟丁酸脱氢酶(HBDH)、肌酸激酶同工酶(CKim)、乳酸脱氢酶(LDH)升高,超敏C-反应蛋白(hCRP)升高,嗜酸性粒细胞(EOS)降为“0”,根据“恙虫病积分诊断量表”、恙虫病东方体抗体阳性、焦痂恙虫病东方体阳性结果,临床和病原学诊断为“TD伴MOD”。入院第3天反复发生UGB,实验室检查显示ALT、AST、BUN、Scr、PCT、HBDH、CKim、LDH、hCRP进一步升高,血小板(PLT)迅速下降,凝血功能异常,并发生MOFS(循环衰竭、呼吸衰竭),临床诊断为“TD合并MOF(循环衰竭、呼吸衰竭)、MOD(肝脏、肾脏、血液系统)和脓毒血症”,在气管插管辅助呼吸、抗休克、器官保护下,经上腹部多层螺旋CT和数字减影血管造影术检查确定为胃左动脉分支出血致胃出血,对出血血管栓塞止血。恢复期胃镜检查提示出血性溃疡,组织病理学显示炎症反应。本文在国内外首次报道TD致UGB、MOF、MOD、脓毒血症的临床治愈病例。结论TD可引起出血性溃疡,导致UGB、MOF,准确病原学治疗,及时介入止血治疗是抢救成功的关键。     

De novo minimal change disease associated with reversible post-transplant nephrotic syndrome. A report of five cases and review of literature

Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be related to a large variety of glomerular lesions. In some of these cases, the transplant biopsy showed no significant glomerular changes and the NS was reversible, but the primary renal disease was not minimal change disease (MCD), suggesting that MCD may develop de novo in renal transplant setting. Knowledge of this entity, however, is limited. Among 67 cases of post-transplant NS encountered in a 12-yr period, five were found to be associated with de novo MCD. A critical review of the literature revealed nine additional cases of de novo MCD. The data from these 14 cases show that patients with de novo MCD had a large variety of primary renal diseases but MCD or focal segmental glomerulosclerosis was not among them. Eight of the 14 transplanted kidneys (60%) were from living related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3-76 g/d) developed immediately or shortly after transplantation (within 4 months for all reported cases, except for one at 24 months). The serum creatinine when NS was first diagnosed was normal or mildly elevated, but acute renal failure occurred in three patients. On biopsy, the glomeruli were normal or, more frequently, displayed mild, focal segmental mesangial sclerosis, hypercellularity, deposition of IgM/C3, or accumulation of mononuclear inflammatory cells in some glomerular capillaries. The tubulointerstitial compartment was normal in cases with normal renal function; displayed mild acute and/or chronic rejection that correlated with a mildly elevated serum creatinine; or showed acute changes including acute rejection, acute tubular necrosis, or acute cyclosporin A toxicity, which accounted for both acute renal failure at presentation and its subsequent reversibility. Under various treatments, including increased steroids, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers, sustained remission of NS was achieved in 13 cases, within a year (0.5-12 months) in 10 and later (24, 34 and 98 months, respectively) in three. In the remaining case, the patient died of septic shock 2 months after transplantation. After remission of the NS, the grafts functioned well without or with minimal proteinuria for several years. De novo MCD has characteristic clinical and pathologic features. It represents an important but hitherto underemphasized cause of post-transplant NS, which is potentially reversible and does not adversely affect the renal transplants.     

Adult and paediatric patients with minimal change nephrotic syndrome show no major alterations in glomerular expression of sulphated heparan sulphate domains.

BACKGROUND: Minimal change nephrotic syndrome (MCNS) is the most frequent form of nephrotic syndrome in childhood. In the glomerular basement membrane (GBM) of adult patients with MCNS, a reduced expression of a specific heparan sulphate (HS) domain has been reported. In children with MCNS, urinary activity of the HS-degrading enzyme heparanase was increased. It is, therefore, possible that a decreased GBM HS expression is associated with the pathogenesis of proteinuria in patients with MCNS. METHODS: In this study, HS in glomeruli of five adult and six paediatric patients with MCNS were analysed by immunofluorescence staining using four different antibodies, each defining a specific sulphated HS domain. The pediatric patients were subdivided into three groups depending on the presence or absence of podocyte foot process effacement, the level of proteinuria and prednisone administration at the time of the biopsy. In addition, kidneys of rats with adriamycin nephropathy (ADRN), a model for MCNS, were included in the study. RESULTS: Expression of sulphated HS domains was not aberrant in adult or paediatric patients compared with control subjects. Children with and without proteinuria had the same HS content. In contrast, rats with ADRN showed a decreased glomerular expression of sulphated HS domains. CONCLUSIONS: These results suggest that in patients with MCNS proteinuria is not associated with major changes in glomerular expression of sulphated HS domains.