Dietmar Zdunek

Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary albumin excretion 1141 mg/24 h. Patients with the highest compared with the lowest quartile of urinary NGAL at baseline had higher urinary KIM-1 levels and a significant decrease in their GFR each year. Using linear regression analysis, we found that elevated urinary NGAL and KIM-1 concentrations were associated with a faster decline in GFR, but not after adjustment for known promoters of progression. Urinary LFABP was not related to decline in GFR. Losartan treatment (100 mg/day) reduced urinary KIM-1 by 43% over a 12-month period. Thus, urine biomarker measurements in patients with type 1 diabetic nephropathy did not provide additional prognostic information to that of known progression promoters.

Effect of GB Virus C Coinfection on Response to Antiretroviral Treatment in Human Immunodeficiency Virus–Infected Patients

To study how GB virus C (GBV-C) coinfection affects the response to highly active antiretroviral therapy (HAART), 146 human immunodeficiency virus (HIV)-infected patients were tested for GBV-C RNA and antibodies against GBV-C E2 protein, and responses to HAART were evaluated. GBV-C-infected patients exhibited a complete virological response to HAART more often than patients without [correction] GBV-C and had a greater increase in median CD4 cell count and a marginally greater median HIV RNA level decrease. This association was found to be independent of baseline CD4 cell count and plasma HIV RNA, which indicates that an association exists between GBV-C infection and response to HAART.

Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients.

UNLABELLED Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria. METHODS We performed a follow-up study, follow-up median (range) 3.5 (1-5) years. At baseline u-NGAL, u-KIM1 and p-FGF23 (ELISA) was measured and patients were followed yearly with estimated(e)-GFR (MDRD) and u-albumin. RESULTS We included 177 patients (44 women), mean age (SD) 59 (9) years. eGFR 90 (24) ml/min/1.73 m(2) at baseline, u-albumin: median (interquartile range) 104 (39-238) mg/24 h. Patients with levels of u-KIM1 in the highest quartile had a greater decline in eGFR than patients with the lowest quartile 6.0 (5.4) versus 3.2 (5.5) ml/min/1.73 m(2) per year (p=0.02). u-NGAL in the highest versus lowest quartile eGFR decline: 5.1 (4.7) and 2.8 (7.1)ml/min/1.73 m(2) per year (p=0.07). Higher values of u-NGAL and u-KIM1 were associated with enhanced decline in eGFR (R=0.16 and R=0.19, p<0.05), however not after adjustment for progression promoters. p-FGF23 was not predictive of decline in eGFR. CONCLUSION Higher levels of markers of tubular damage are associated with a faster decline in eGFR. However, since this is not independent of known progression promoters, measurement of tubular markers does not give additional prognostic information.

Urinary L-FABP and anaemia: distinct roles of urinary markers in type 2 diabetes.

Eur J Clin Invest 2010; 40 (2): 95–102

Effect of stress-induced reversible ischemia on serum concentrations of ischemia-modified albumin, natriuretic peptides and placental growth factor

SummaryObjectiveThere is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis.MethodWe measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing.ResultsOf the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p < 0.05; NT-pro ANP 732.5 (470.0/ 1220.0) pg/mL vs 1470.0 (694.0/ 1910.0) pg/mL, p < 0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects.ConclusionThe elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoced ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.

High sensitive troponin T and heart fatty acid binding protein: Novel biomarker in heart failure with normal ejection fraction?: A cross-sectional study

BackgroundHigh sensitive troponin T (hsTnT) and heart fatty acid binding protein (hFABP) are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF). We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF).MethodsWe analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD), and 30 controls with normal diastolic function. Patients were classified to have HFnEF when the diagnostic criteria as recommended by the European Society of Cardiology were met.ResultsLevels of hs TnT and hFABP were significantly higher in patients with asymptomatic LVDD and HFnEF (both p < 0.001) compared to controls. The hsTnT levels were 5.6 [0.0-9.8] pg/ml in LVDD vs. 8.5 [3.9-17.5] pg/ml in HFnEF vs. <0.03 [< 0.03-6.4] pg/ml in controls; hFABP levels were 3029 [2533-3761] pg/ml in LVDD vs. 3669 [2918-4839] pg/ml in HFnEF vs. 2361 [1860-3081] pg/ml in controls. Furthermore, hsTnT and hFABP levels were higher in subjects with HFnEF compared to LVDD (p = 0.015 and p = 0.022).ConclusionIn HFnEF patients, hsTnT and hFABP are elevated independent of coronary artery disease, suggesting that ongoing myocardial damage plays a critical role in the pathophysiology. A combination of biomarkers and echocardiographic parameters might improve diagnostic accuracy and risk stratification of patients with HFnEF.

NT-proBNP is increased in healthy pregnancies compared to non-pregnant controls

Serum concentrations of the amino‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) may be used to monitor cardiac function during pregnancy but normal values are not established for this purpose. Therefore, we investigated NT‐proBNP in normotensive healthy pregnancies compared to a non‐pregnant control group. Serum NT‐proBNP was measured in 94 normotensive, healthy pregnant women (32±6 years) every five weeks beginning from 12th gestational week (GW) in a longitudinal study and compared to a non‐pregnant control group of 521 women (32±7 years). Pooled median serum NT‐proBNP levels (25th; 75th percentile) were significantly higher in pregnant women compared to non‐pregnant women (56 (33; 95) pg/ml vs. 38 (22; 62) pg/ml (p<0.001)). NT‐proBNP increased during pregnancy to 73 (51; 124) pg/ml in the 11+6 to 15+6 GW (p<0.001). However, NT‐proBNP levels from 23+0 GW towards term were comparable to non‐pregnant controls. NT‐proBNP is significantly elevated in healthy pregnancies until mid‐pregnancy. As preeclampsia and gestational hypertension are associated with increased NT‐proBNP, our results have to be considered in future diagnostic approaches using NT‐proBNP for these pathologic conditions.

Active or Prior GB Virus C Infection Does Not Protect against Vertical Transmission of HIV in Coinfected Women from Tanzania

To determine whether GB virus C (GBV-C) infection is associated with protection against vertical transmission of human immunodeficiency virus (HIV), we tested 186 HIV-positive pregnant women for GBV-C. Neither active nor prior GBV-C infection was associated with a lower rate of HIV acquisition among infants. Thus, GBV-C does not appear to protect against perinatal HIV acquisition.

The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP

Abstract Aim. Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP). Methods. A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria. After 2 months washout of all antihypertensive medication except bendroflumethiazid, patients were treated in random order with irbesartan 300, 600 and 900 mg for 2 months. End points. Urinary tubular markers at baseline and after each treatment period (ELISA), 24-h blood pressure, glomerular filtration rate (GFR, 51CrEDTA) and 24-h urine albumin excretion (UAER). Results. Fifty-two patients completed the study (41 male). Age (mean (SD)): 58(10) years and diabetes duration 13(8) years. Baseline GFR was 101(24) and UAER (geometric mean [95%CI]) 133 (103–172) mg/24 h. With increasing doses of irbesartan (300, 600, 900 mg) u-KIM1 was reduced with 15%, 10% and 15% (p = 0.07 between 300 mg vs. baseline and no difference between doses). Patients with high u-KIM1 at baseline (above median) had a 32% reduction in u-KIM1 during treatment (p = 0.01). No significant decline in U-NGAL compared to baseline. U-LFABP increased during treatment (p < 0.01). Conclusions. Irbesartan treatment reduced levels of the tubular marker u-KIM1 in patients with type 2 diabetes and microalbuminuria. u-NGAL changed insignificantly and u-LFABP increased. More studies with longer follow up are needed to determine the role of tubular markers in monitoring treatment effect and prediction of prognosis in diabetic nephropathy.

Hepatitis G virus RNA is common in AIDS patients' plasma but is not associated with abnormal liver function tests or other clinical syndromes

Hepatitis G virus (HGV) is a new virus found in 1% to 4% of blood from all donors but is more prevalent in some immunocompromised groups, with unclear clinical significance. Frozen plasma samples from 192 AIDS patients were tested for HGV RNA; 44 (23%) were positive. Positive patients did not differ from negative patients in age, gender, race, HIV infection risk factors, nor blood transfusion exposure. Hepatitis BsAg was associated with HGV infection (odds ratio [OR] = 7.7; 95% confidence interval [CI], 2.4-25.0) but hepatitis C antibody was not. Mean values for liver function tests and hematologic values did not differ significantly between the groups nor did the occurrence of certain recognized AIDS-related complications. Mean CD4+ cell counts and HIV-1 plasma RNA levels were comparable in the two groups, but the mean circulating CD8+ cell count in the HGV-positive group (853+/-458 cells/microL) was higher than in the negative group (682+/-457 cells/microL; p = .03). Hepatitis G virus, although common in AIDS patients, does not appear to alter the course of AIDS nor appear as a distinct hepatitis syndrome.