Proteinuria prevalence in insulin-treated patients: prediction of need for end-stage renal failure treatment

In the Dundee Diabetic clinic area (population circa 250,000), a population-based survey of the prevalence of proteinuria in diabetic patients treated with insulin showed that 9.4% of such patients had persistent proteinuria. The percentage of males with proteinuria was 11.4%, against 7.2% of females. An additional 5.2% of patients had proteinuria observed once, but did not meet the criteria for persistent proteinuria. No result was available in 10% of patients for a variety of reasons. Not every patient with diabetes and persistent proteinuria will progress to end-stage renal failure, but consideration of the group as a whole allows predictions based on published reports, to be made of the likely future incidence of renal failure, and hence future need for renal replacement services. We estimate that over the next decade two patients per 125,000 total population will develop renal failure each year. If survival is unchanged, there could be two or three times that number on treatment at any time.     

缬沙坦联合福辛普利治疗IgA肾病蛋白尿的疗效观察

目的 观察缬沙坦联合福辛普利治疗IgA肾病蛋白尿的疗效及安全性.方法 选择IgA肾病患者60例,随机分成治疗组32例和对照组28例.治疗组给予缬沙坦联合福辛普利治疗;对照组单用福辛普利治疗.疗程为6个月,观察治疗前后24 h尿蛋白定量及药物不良反应情况.结果 治疗后治疗组24 h蛋白尿改善显著优于对照组（P＜0.01）;治疗组总有效率显著高于对照组（P＜0.01）;两组患者用药后不良反应发生率无显著差异（P＞0.05）.结论 缬沙坦联合福辛普利治疗IgA肾病蛋白尿疗效显著优于单用福辛普利,且不良反应并无增加.     

CD+4T淋巴细胞在激素敏感型肾病综合征发病中的作用研究

目的　明确激素敏感型肾病综合征T淋巴细胞致病因子的亚群来源 ,探讨CD 4T淋巴细胞在本病发病中的作用。方法　采用间接免疫荧光染色法测定肾病综合征患儿外周血CD 4、CD 8T细胞百分率 ,以及CD 4/CD 8比值 ;磺柳酸比浊法测定经大鼠尾静脉注射抗体结合 补体介导溶解法分离的患儿CD 4和CD 8T淋巴细胞培养上清液后的大鼠尿蛋白含量 ,电镜观察其肾小球超微结构与基底膜上阴离子位点改变。结果　 (1)肾病综合征活动期患儿外周血CD 4T淋巴细胞百分率为(33 4± 2 4) % ,与正常儿童比较差异无显著性 (P >0 0 5 ) ;CD 8T淋巴细胞百分率为 (15 5±4 5 ) % ,比正常儿显著降低 (P <0 0 1) ;CD 4/CD 8比值为 (2 2± 0 3) % ,比正常儿显著升高(P <0 0 1)。(2 )注射患儿CD 4T淋巴细胞培养上清液后 ,大鼠尿蛋白排泌量在 0～ 8h时间段由注射前的 (3 9± 0 6 )mg/ 2 4h显著增加到 (13 1± 4 3)mg/ 2 4h(P <0 0 0 1)。注射患儿CD 8T淋巴细胞培养上清液后 ,大鼠尿蛋白排泌量无明显变化 (P >0 0 5 )。蛋白尿大鼠出现肾小球上皮细胞足突融合、基底膜上阴离子位点显著减少。结论　注射患儿CD 4T淋巴细胞培养上清液可使大鼠出现一过性蛋白尿 ;CD 4T淋巴细胞功能紊乱 ,分泌致病因子是激素敏感型肾病综合     

雷帕霉素加重蛋白负荷肾病大鼠肾脏的损害及氯沙坦的保护作用

目的 观察雷帕霉素对蛋白负荷肾病大鼠肾脏组织和肾功能的影响及氯沙坦的保护作用，并探讨相关机制。 方法 采用牛血清蛋白（BSA）诱导Wistar雌性大鼠建立蛋白负荷的肾病大鼠模型，根据处理不同分成模型对照组、雷帕霉素组（单纯使用雷帕霉素，Rapa组）和氯沙坦组（同时使用雷帕霉素和氯沙坦）。检测不同时间点各组大鼠的尿蛋白量（24 h）和肾功能水平，并对肾组织进行光镜和电镜检查。 结果 实验第7 天，Rapa组和氯沙坦组大鼠尿蛋白量（24 h）均显著高于模型组（均P < 0.05），但氯沙坦组大鼠尿蛋白量（24 h）较Rapa组有明显缓解（P < 0.05）。实验第14天，Rapa组大鼠尿蛋白量（24 h）仍显著高于模型组（P <0.05），而氯沙坦组与模型对照组间的尿蛋白量（24 h）差异已无统计学意义。肾组织光镜检查显示Rapa组大鼠肾小管管腔中的蛋白管型明显增加；而氯沙坦组的蛋白尿和蛋白管型较Rapa组有明显减少；电镜结果显示Rapa组肾脏可见明显的肾小球局灶性足突融合。 结论 雷帕霉素增加蛋白负荷肾病大鼠的蛋白尿水平，其主要机制可能与雷帕霉素损伤肾小球足细胞后导致肾小球滤过屏障的改变有关；氯沙坦可以减轻雷帕霉素所致的大量蛋白尿。     

西藏地区糖尿病肾病临床特点分析

目的 分析西藏地区2型糖尿病肾病(DN)的临床特点。 方法 回顾分析2001年5月至2006年10月间在我科住院的306例2型糖尿病（DM）患者的临床资料。 结果 306例DM患者包括151例DN和155例非DN患者，根据尿白蛋白及Scr水平，DN组患者再分为微量白蛋白尿组、临床蛋白尿组和肾功能不全组。DN组尿微量白蛋白、Scr和血、尿β2微球蛋白(MG)均较非DN组显著增高（均P < 0.01）；且尿微量白蛋白与收缩压、血β2-MG呈正相关（r = 0.187， P < 0.05； r = 0.297， P < 0.01），而与GFR呈负相关（r = －0.287，P < 0.01）。DN组高血压发生率高（60.27％），血压显著高于非DN组（P < 0.01），且以收缩压更显著。DN组发生尿毒症者14例（9.27％），死亡8例（5.30％），其中5例死于尿毒症；并发糖尿病视网膜病变20例(13.25%)；发生心脑血管意外者6例(3.97%)。 结论 西藏地区2型糖尿病肾病早期即有明显的蛋白尿、血压及血、尿β2-MG增高，后期GFR急剧下降且并发症多而严重。     

A Prospective Randomised Comparative Study on the Influence of Cyclosporin and Azathioprine on Renal Allograft Survival and Function

To study the effectiveness and nephrotoxic side-effects of cyclosporinA (CsA) in renal transplant recipients, a prospective randomisedtrial was designed to compare CsA with azathioprine (Aza). Eachtreatment group consisted of 40 patients; in the CsA group,18 were randomly selected for conversion to Aza after 3 months.The 1-year graft survival for CsA-treated patients was 87% comparedwith 66% for the Aza group (P=0.033). Anti-rejection therapywas administrated to 78% of the patients in the Aza group and47% of those in the CsA group (P<0.01). There was no differencein the incidence of primary non-functioning kidneys, cytomegalovirusinfections, hypertension, or degree of proteinuria between thetwo treatment groups. At 3 months the mean creatinine clearance was 42±2 ml/min(mean±SEM) for the CsA group compared with 56±4ml/min for the Aza group (P<0.01), whereas the mean creatinineclearances at 6 months for both the converted and the non-convertedCsA-treated patients did not differ from that found in the Aza-treatedgroup. At 1 year, the mean creatinine clearance for CsA-treatedpatients who were converted to Aza was higher than that foundfor Aza treated patients (62±7 vs 50±6 ml/min;P<0.05). Furthermore, the increment in creatinine clearanceobserved after conversion from CsA to Aza at 3 months showeda linear relationship (r=0.9061) with the CsA trough levelsbefore discontinuation of the drug. This indicates that CsA treatment induces a dose-dependent,nephrotoxic side-effect which is probably reversible.     

Paradoxical fall in proteinuria during pregnancy in an LCAT-deficient patient—A case report

A 29-year-old lady was diagnosed with lecithin:cholesterol acyltransferase (LCAT) deficiency having presented with bilateral corneal clouding, severely reduced high density lipoproteins cholesterol, and proteinuria. She is a compound heterozygote with two LCAT gene mutations, one of which is novel, c.321C>A in exon 3. Surprisingly, the level of proteinuria significantly improved during pregnancy, despite stopping the angiotensin-converting enzyme inhibitor. However, LCAT concentration and activity remained identical during pregnancy and postpartum. Her pregnancy was complicated by rising triglyceride levels from the second trimester requiring treatment with omega-3 fatty acid and fenofibrate. In the last trimester, a further complication arose when she became hypertensive and proteinuria worsened. She was diagnosed with pre-eclampsia and had an emergency cesarean section at 39 weeks delivering a healthy baby. This case adds to the knowledge of the pathophysiology of LCAT deficiency during pregnancy and will be useful in future patient management.     

Renal involvement in PMM2-CDG,a mini-review

Phosphomannomutase 2 deficiency (PMM2-CDG) is the most common N-linked glycosylation disorder. The majority of patients present with a multisystem phenotype, including central nervous system involvement, hepatopathy, gastrointestinal and cardiac symptoms, endocrine dysfunction and abnormal coagulation. Renal abnormalities including congenital malformations and altered renal function are part of the multisystem manifestations of congenital disorders of glycosylation.We reviewed the literature on 933 patients with molecularly and/or enzymatically confirmed PMM2 deficiency to evaluate the incidence of renal involvement in PMM2-CDG.Renal abnormalities were reported in 56 patients. Congenital abnormalities were present in 41 out of these 55. Cystic kidney and mild proteinuria were the most common findings. One of the most severe renal manifestations, congenital nephrotic syndrome, was detected in 6 children. Renal manifestations were not associated with the presence of specific PMM2 alleles.This review summarizes the reported renal abnormalities in PMM2-CDG and draws attention to the pathophysiological impact of abnormal glycosylation on kidney structure and function.     

Crumbs homolog 2 mutation in two siblings with steroid-resistant nephrotic syndrome: Two case reports

BACKGROUND Crumbs homolog 2 (CRB2) is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes; mutations can directly lead to steroid-resistant nephrotic syndrome (SRNS). However, the characteristics of nephrotic syndrome (NS) caused by CRB2 mutations have not been described.CASE SUMMARYWe report a novel compound heterozygous mutation of the CRB2 gene in two siblings with SRNS. The two siblings had edema, proteinuria, hypoproteinemia and hyperlipidemia. Both their father and mother had normal phenotypes (no history of NS). Whole exon sequencing (WES) of the family showed a novel compound heterozygous mutation, c.2290 (exon 8) C > T and c.3613 (exon 12) G > A. Glucocorticoid therapy (methylprednisolone pulse therapy or oral prednisone) and immunosuppressive agents (tacrolimus) had no effect. During a 3-year follow-up after genetic diagnosis by WES, proteinuria persisted, but the patient was healthy.CONCLUSION CRB2 mutations related to SRNS often occur in exons 7, 10, and 12. Clinical manifestations of SRNS caused by CRB2 mutations are often less severe than in other forms of SRNS.     

依普利酮对糖尿病肾病患者微血管病变及尿蛋白含量的影响

[目的]探讨依普利酮治疗糖尿病肾病患者的疗效及对微血管病变及尿蛋白含量影响.[方法]选择本院2013年1月至2014年10月期间收治83例糖尿病肾病患者作为研究对象,采用随机数字表法分为观察组(n=42)与对照组(n=41).对照组应用螺内酯治疗,观察组用依普利酮治疗,比较两组治疗前后24 h尿蛋白、尿微量白蛋白(uAlb)、尿免疫球蛋白G(uIgG)、血浆层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)水平变化.[结果]两组治疗前24 h尿蛋白,uAlb与uIgG及LN、PCⅢ与CⅣ水平相比较差异均无显著性(P>0.05),治疗后各项指标均降低,组内前后相比较差异有显著性(P<0.05).同时观察组各项指标治疗后比对照组改善幅度更大,且两组间相比较差异有显著性(P<0.05).[结论]依普利酮为新型选择性醛固酮拮抗剂,在糖尿病肾病患者中应用可显著降低患者尿蛋白量并改善微血管病变,同时抑制并逆转肾脏纤维化,其效果理想,值得借鉴推广.