南征教授治疗糖尿病肾病新路径——调散膏,达膜原

中国糖尿病患者人数9240万，发病率达9．7％，可见糖尿病已严重威胁着人们的身体健康，然而目前2型糖尿病患者发生糖尿病肾病（DN）的几率高达20％。50％。DN是糖尿病最常见的微血管病变之一，预后差、致残率高[2]，而且DN已成为导致终末期肾病首要病因，又是引起糖尿病患者死亡的主要原因。DN病因病机复杂，病程漫长，

Correlation between podocyte excretion and proteinuria in diabetic nephropathy patients

Objective： To observe the podocyte injury in diabetic nephropathy （DN） patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between podocyte excretion and proteinuria, blood glucose, serum creatinine in different phases in DN patients. Methods： Urinary podocytes and the podocalyxin （PCX） expression state of podocytes in glomeruli were identified and observed by indirect immunofluorescent method. The DN patients were divided into three groups according to the volume of proteinuria, namely small, medium and large volume proteinuria groups. The podocytes in the urine of every group were calculated. The DN patients were divided into five groups according to the chronic kidney disease （CKD） phases, then the positive podocytes in urine were calculated. Meanwhile, the 24-hour protein in urine, fasting blood glucose （FBG） and the serum creatinine of DN patients were tested. The correlations among the proteinuria, serum creatinine, FBG and the number of positive podocytes in the urine of DN patients were statistically analyzed. Results： Urinary positive podocytes were found in 88% of the patients with DN, whereas podocytes were found in 0% of patients with minimal changed disease （MCD） and healthy cases. The expression of PCX was absent in DN patients. In contrast, PCX was expressed integrally in MCD patients. The positive podocytes was 1.49±0.95/ml in small-volume proteinuria group, 2.15±0.70/ml in the medium-volume proteinuria group, and 3.48±1.27/ml in the large-volume proteinuria group. There was no significant difference between the small- and medium- volume proteinuria groups, and there were significant differences between other groups （P〈0.05）. The positive podocyte number tended to increase as proteinuria was increased. By Pearson analysis, the correlation between podocyte number and proteinuria was podocytes in urine from different groups of DN patients, CKD pc I sitive statistically. The difference of the number of positive -V group was significant statistically. The correlation between serum creatinine of CKD Ⅰ -Ⅲ group and positive podocytes in urine was positive statistically. The correlation between serumcreatinine of CKD Ⅳ- Ⅴ group and positive podocytes in urine was not significant statistically. The correlation between FBG and positive podocytes in urine was not significant either. Conclusion： The mechanism of the podocyte injury in DN patients is present. The podocyte injury in DN may positively correlate to proteinuria and serum creatinine of CKD Ⅰ -ⅢDN patients, but not to the FBG and serum creatinine of CKD Ⅳ-Ⅴ patients.

Silent diabetic nephropathy

AIM： To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy （DN） and its possible associated factors.METHODS： Clinical and histological data of 60 pa-tients diagnosed with diabetic nephropathy were retro-spectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The fnal event was defned as renal replacement ther-apy （RRT） initiation or progression of chronic kidney disease （CKD）, according to the KDIGO 2012 defnition of a decrease in CKD category and a decrease in GFR of 25% or more. RESULTS： A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a mean age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, al-though in 13 patients, it was less than 5 years. A total of 62% of patients reached the fnal event in a mean period of 3.4 years （95%CI： 2.1-4.7）, with 21 of them requiring dialysis. The factors that were indepen-dently associated with renal survival were estimated glomerular fltration rate （eGFR） at the time of biopsy, cardiovascular disease （CVD） history and HbA1c less than 7%. Therefore, for each 10 mL/min per 1.73 m2 reduction in eGFR, we obtained a DN progression risk of HR = 2 （1.3-3.0） （P = 0.001）; patients with CVD were at greater risk for DN progression （HR = 2.8, 1.1-7.1, P = 0.032）, and CKD patients with HbA1c 〈 7% demonstrated greater renal risk than patients with HbA1c ≥ 7%, with an HR of 2.9 （1.0-8.4） （P = 0.054）.CONCLUSION： A past history of CVD is a risk fac-tor for DN progression. Levels of HbA1c less than 7% could favor an eGFR decrease in these patients.

Exercise-induced albuminuria and circadian blood pressure abnormalities in type 2 diabetes

AIMTo investigate the relationship between circadian vari-ations in blood pressure （BP） and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes （T2D） patients.METHODSWe conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical pro-teinuria and normal creatinine clearance. In each parti-cipant, we recorded the BP using ambulatory bloodTankeu AT et al . Exercise-induced albuminuria and BP in T2DMpressure monitoring （ABPM） for 24-h, and albuminuria at rest and after a standardized treadmill exercise.RESULTSWe enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure （SBP） of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg （ P = 0.004）, and mean diurnal diastolic blood pressure （DBP） of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg （ P = 0.002）. There was a signifcant difference between albuminuria at rest [median = 23 mg, interquartile range （IQR） = 10-51] and after exercise （median = 35 mg, IQR = 23-80, P 〈 0.001）. Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components （128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure）, as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP （83 vs 86, P = 0.03） than resting albuminuria.CONCLUSIONExercise induced albuminuria is associated with anincrease in nocturnal BP values in T2D patients.

Vascular response to vasodilator treatment in microalbuminuric diabetic kidney disease

Under common practice, the conventional diagnostic marker such as microalbuminuria determination does not recognized early stage of diabetic kidney disease （normoalbuminuria, chronic kidney disease stage 1, 2）; due to the insensitiveness of the available marker. Treat-ment at later stage （microalbuminuria） simply slows the renal disease progression, but is rather diffcult to restore the renal perfusion. Intrarenal hemodynamic study in these patients revealed an impaired renal per-fusion and abnormally elevated renal arteriolar resis-tances. Treatment with vasodilators such as angiotensin converting enzyme inhibitor and angiotensin receptor blocker fails to correct the renal ischemia. Recent study on vascular homeostasis revealed a defective mecha-nism associated with an impaired nitric oxide production which would explain the therapeutic resistance to va-sodilator treatment in microalbuminuric diabetic kidney disease. This study implies that the appropriate thera-peutic strategy should be implemented at earlier stage before the appearance of microalbuminuria.

Unexpected hypercalcemia in a diabetic patient with kidney disease

We report a case of a diabetic patient with progressive chronic kidney disease and unexplained hypercalcemia. This unusual presentation and the investigation of all possible causes led us to perform a renal biopsy. The systemic sarcoidosis diagnosis was confirmed by the presence of interstitial multiple granulomas composed of epithelioid and multinucleated giant cells delimited by a thin fbrous reaction, and by pulmonary computed tomography finding of numerous lumps with ground-glass appearance. Sarcoidosis most commonly involves lungs, lymph nodes, skin and eyes, whilst kidney is less frequently involved. When it affects males it is characterized by hypercalcemia, hypercalciuria, and progressive loss of renal function. Early treatment with steroids allows for a gradual improvement in renal function and normalization of calcium serum values. Otherwise, the patient would quickly progress to end stage renal disease. Finding of hypercalcemia in a patient with renal failure must alert physicians because it may be a sign of several pathological entities.