Proteomic analysis for the assessment of diabetic renal damage in humans

2004 ◽  
Vol 107 (5) ◽  
pp. 485-495 ◽  
Author(s):  
Harald MISCHAK ◽  
Thorsten KAISER ◽  
Michael WALDEN ◽  
Meike HILLMANN ◽  
Stefan WITTKE ◽  
...  

Renal disease in patients with Type II diabetes is the leading cause of terminal renal failure and a major healthcare problem. Hence early identification of patients prone to develop this complication is important. Diabetic renal damage should be reflected by a change in urinary polypeptide excretion at a very early stage. To analyse these changes, we used an online combination of CE/MS (capillary electrophoresis coupled with MS), allowing fast and accurate evaluation of up to 2000 polypeptides in urine. Employing this technology, we have examined urine samples from 39 healthy individuals and from 112 patients with Type II diabetes mellitus and different degrees of albumin excretion rate. We established a ‘normal’ polypeptide pattern in the urine of healthy subjects. In patients with Type II diabetes and normal albumin excretion rate, the polypeptide pattern in urine differed significantly from normal, indicating a specific ‘diabetic’ pattern of polypeptide excretion. In patients with higher grade albuminuria, we were able to detect a polypeptide pattern indicative of ‘diabetic renal damage’. We also found this pattern in 35% of those patients who had low-grade albuminuria and in 4% of patients with normal albumin excretion. Moreover, we could identify several of the indicative polypeptides using MS/MS sequencing. We conclude that proteomic analysis with CE/MS permits fast and accurate identification and differentiation of polypeptide patterns in urine. Longitudinal studies should explore the potential of this powerful diagnostic tool for early detection of diabetic renal damage.

1997 ◽  
Vol 25 (2) ◽  
pp. 81-86 ◽  
Author(s):  
G Sorrenti ◽  
M Grimaldi ◽  
N Canova ◽  
E Palazzini ◽  
N melchionda

The aim was to investigate sulodexide as a possible therapeutic tool for treating micro- and macroalbuminuria in diabetic patients. Fifteen patients (13 micro- and 2 macroalbuminuric) with Type II diabetes, were treated with 600 lipoprotein-lipase releasing units of sulodexide by the intramuscular route, daily for 28 days, and followed up for 2 months. The main evaluation parameter was the albumin excretion rate. At the end of treatment, six of the 13 microalbuminuric patients showed a decrease in the albumin excretion rate, which increased again in three of the six during follow-up. In the two macroalbuminuric patients the albumin excretion rate decreased at the end of treatment and remained unchanged after a further 2 months. Overall analysis (15 patients) showed a significant decrease ( P < 0.05) in the albumin excretion rate compared with baseline. Metabolic control and blood pressure remained unchanged during the entire period of study. No adverse events were registered. It is concluded that sulodexide administration has a favourable effect in reducing the albumin excretion rate in Type II diabetic patients with micro- and macroalbuminuria.


Diabetologia ◽  
1999 ◽  
Vol 42 (11) ◽  
pp. 1359-1366 ◽  
Author(s):  
C. M. Forsblom ◽  
T. Kanninen ◽  
M. Lehtovirta ◽  
C. Saloranta ◽  
L. C. Groop

1995 ◽  
Vol 9 (4) ◽  
pp. 272-276 ◽  
Author(s):  
Sianna Panagiotopoulos ◽  
Trudy Jeanne Smith ◽  
G.Peter Aldred ◽  
Elizabeth Jane Baker ◽  
Carolyn Jane Jacklin ◽  
...  

1986 ◽  
Vol 23 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Sebastiano Bruno Solerte ◽  
Marisa Fioravanti ◽  
Anna Bozzetti ◽  
Nicola Schifino ◽  
Anna Linda Patti ◽  
...  

2018 ◽  
Vol 314 (3) ◽  
pp. R323-R333 ◽  
Author(s):  
Brittany Wade ◽  
Galina Petrova ◽  
David L. Mattson

The present study assessed the importance of immunity in angiotensin (ANG) II (5 ng·kg−1·min−1 iv)-mediated hypertension in Dahl salt-sensitive (SS) rats and SS rats deficient in T and B lymphocytes (SSRag1−/−) fed a 0.4% NaCl diet. Baseline mean arterial blood pressure (MAP) was not different between groups. ANG II infusion significantly increased MAP in both groups, although MAP increased more rapidly in SS rats, and the maximal MAP achieved was significantly greater in SS than SSRag1−/− rats (190 ± 3 vs. 177 ± 3 mmHg) after 12 days. Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of ANG lI infusion in SS (from 32 ± 4 to 81 ± 9 mg/day) and SSRag1−/− (from 12 ± 2 to 51 ± 8 mg/day) rats; albumin excretion rate was significantly different between SS and SSRag1−/− rats at all points measured. After 9 days of recovery from ANG II, MAP was decreased to a greater extent in SSRag1−/− than SS rats (143 ± 5 vs. 157 ± 8 mmHg) compared with the peak MAP during ANG II infusion. At this same time point, albumin excretion rate was significantly lower in SSRag1−/− than SS rats (42 ± 8 vs. 66 ± 7 mg/day). Further studies demonstrated an increase in CD45+ total leukocytes, CD11b/c+ macrophages/monocytes, and CD3+ T cells in kidneys of ANG II- compared with vehicle-treated SS rats. The present data suggest that infiltrating T cells in the kidney exacerbate renal damage in ANG II-induced hypertension in SS rats maintained on a 0.4% NaCl diet, similar to results observed with a salt stimulus in SS rats.


1987 ◽  
Vol 24 (2) ◽  
pp. 149-155 ◽  
Author(s):  
Giuseppa Perdichizzi ◽  
Domenico Cucinotta ◽  
Rosalba Fera ◽  
Enrico Cesare ◽  
Salvatore Campo ◽  
...  

1994 ◽  
Vol 87 (4) ◽  
pp. 421-425 ◽  
Author(s):  
J. G. Fox ◽  
J. D. Quin ◽  
D. St. J. O'Reilly ◽  
J. M. Boulton-Jones

1. Glomerular charge selectivity was assessed using the ratio of the clearance of pancreatic isoamylase to the clearance of the more anionic salivary isoamylase (CPAm/CSAm) in 53 patients with primary glomerulopathies (minimal change nephropathy, idiopathic membranous nephropathy, IgA nephropathy) and a wide range of albumin excretion rates and in 31 healthy subjects. Fractional clearances of pancreatic and salivary isoamylases (FCPAm, FCSAm) and of albumin (FCAlb) were also measured. 2. CPAm/CSAm and FCPAm were negatively correlated with FCAlb for the whole patient group (rs = −0.56 and rs = −0.65, respectively, P < 0.0001 for both), but there was no correlation of FCSAm with FCAlb. 3. For patients with near-normal albumin excretion rates (< 100 mg/24 h), there was no difference in CPAm/CSAm between the three types of glomerulopathy or between patients and healthy subjects. 4. These data suggest that glomerular charge selectivity at the size of amylase (which is smaller than albumin) is progressively lost as albuminuria increases from normal to the nephrotic range. Size restriction progressively increases until albuminuria is very heavy. When the albumin excretion rate is near normal, charge selectivity is also normal in the three main forms of primary glomerulopathy.


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