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A case of strongyloidiasis in a patient with membranoproliferative glomerulonephritis is reported. In our patient, strongyloidiasis evolved latently and became overt after corticotherapy, and it turned to be a very severe outcome and life-threatening complications, hyperinfection syndrome and upper digestive tract hemorrhage. Besides its well-known complications, steroid therapy may provide real surprises. The association of this therapy with strongyloidiasis may turn an undiagnosed inactive, chronic form of the disease into an active form within the framework of a hyperinfection syndrome which might lead to death. In our case, the diagnosis of strongyloidiasis was established only after duodenal biopsy was performed for upper digestive tract hemorrhage, which revealed the parasite. It should be underlined that under corticotherapy, the patient evolved favorably with regard to glomerular disease, while strongyloidiasis worsened. The outcome was positive after the patient was treated with albendazole and ivermectin. The diagnosis of strongyloidiasis is sometimes difficult to establish due to the fact that eosinophilia may be absent, while commonly utilized stool examinations may be negative. By analyzing our case, it may be assumed that the immune mechanisms involved in strongyloidiasis do not activate the glomerular nephropathy. On the contrary, these mechanisms seem to have an immunosuppressive effect. The "hygienic hypothesis" also needs to be considered. While on corticotherapy, patients with glomerulonephritis need immunologic and parasitologic monitoring. This is important for other immunodepressing diseases and for immunosuppressive drugs. If the patient has originated in a mining area, as is the case with our patient, or in endemic areas, this monitoring becomes mandatory. The case reflects the complexity of the interrelation between the immune mechanisms in glomerulonephritis and those in parasitic diseases, strongyloidiasis in our case.

The paper highlights the importance of tubular lesions of the solitary kidney (SK), identified and monitored by means of urinary biomarkers, mainly N-acetyl-beta-D-glucosaminidase (NAG), albumin, alpha 1-, and beta 2-microglobulin. It is considered that the assessment of a SK should be performed with four and not three parameters as it was usually done until recently: renal function, proteinuria and blood pressure (BP), to which biomarkers should be added. The solitary kidney can result after nephrectomy for kidney transplantation. In some countries living kidney donors represent the only option for performing kidney transplantation. The SK in living donors has generally a good evolution, although sometimes renal injury manifested by proteinuria, arterial hypertension (AH), or diminution of renal function does occur. Therefore, living donors require attentive monitoring. The SK is considered to have a good evolution (even in donors), in spite of alterations of the above-mentioned clinical and biological parameters. The very infrequent cases who evolve progressively towards renal failure are not predictable, which requires monitoring of all persons with a SK. The SK represents a special situation in case of association with a disease affecting the kidney, such as urinary tract infection (UTI), diabetes mellitus, or systemic lupus erythematosus (SLE). Pregnancy occurring in a person with a SK also needs attentive follow-up. Pregnancy associated diseases, such as preeclampsia occurring in patients with a SK, impose appropriate therapeutic behaviour. The SK remains a particular entity in nephrology which needs to be carefully monitored.

Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

Background: Renal dysfunction is a major determinant of the Model of End-stage Liver Disease (MELD) score. The implementation of the MELD score has shifted allocation of livers to patients with renal dysfunction., Objectives: The aim of our study was the assessment of estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal Disease 4 (MDRD4) method in patients with HBV chronic hepatitis, HCV chronic hepatitis, and cirrhosis (CH) caused by these viruses to detect any differences in renal function among these diseases., Patients and Methods: We performed a cross-sectional analysis of all consecutive patients with HBV chronic hepatitis, HCV chronic hepatitis, and cirrhosis caused by these viruses hospitalized during a 4 year period in the Gastroenterology and Hepatology department of the Emergency County Hospital Timisoara, Romania. The eGFR was assessed by the MDRD4 method. Statistical analysis (unpaired t-test, ANOVA, Chi Square test) was performed using OpenEpi 2.3.1., Results: HBV chronic hepatitis, HCV chronic hepatitis, and cirrhosis secondary to these viruses were associated with a reduction of the GFR. The eGFR was higher in patients with HBV chronic hepatitis than in patients with HCV chronic hepatitis (P &lt; 0.001). Patients with cirrhosis secondary to HBV infection had a higher eGFR than patients with cirrhosis secondary to HCV (P = 0.01). The eGFR of patients with HCV chronic hepatitis was higher than the eGFR of patients with cirrhosis due to this virus (P &lt; 0.001)., Conclusions: Functional renal impairment in diseases caused by HCV was more important than in diseases caused by HBV. The eGFR was statistically lower in cirrhosis secondary to HCV than in HCV chronic hepatitis.

The solitary kidney (SK) is of special interest for practitioners because of the reduced number of nephrons as compared to persons who have 2 kidneys. It undergoes adaptive phenomena of hypertrophy and hyperfiltration that allow long-term evolution, but pathological situations might occur in the remnant kidney. In some persons with a SK, the adaptive phenomena can be associated with proteinuria, arterial hypertension (AH) and diminished Glomerular Filtration Rate (GFR). In very rare situations, diminution of renal function in patients with a SK can progress to end-stage renal disease (ESRD) and, totally exceptionally, it requires renal replacement therapy. The SK can be congenital or acquired. At present patients with a SK address themselves more and more frequently to nephrology services which monitor the evolution of both the congenital and the surgically acquired SK. The congenital SK possesses a higher number of nephrons (75%, as compared to 2 functional kidneys in a healthy person) than the surgically acquired SK - 50% nephrons. This makes adaptive phenomena differ. Secondary lesions sometimes appear later in case of the congenital SK. In other situations, no significant differences between the evolution of the congenital or acquired SK are registered. The congenital solitary kidney is often associated with congenital abnormalities of the kidney and of the urinary tract (CAKUT). This association increases the risk for chronic kidney disease and for evolution towards chronic renal failure. The congenital SK is also often associated with gynaecological and other abnormalities. The acquired solitary kidney can be due to nephrectomy on a pathological kidney which could not be conservatively treated or due to donation of a kidney for renal transplantation. The SK itself sometimes requires partial nephrectomy intervention, for example sparing surgery. Although the evolution is in most cases favorable, it requires attentive monitoring.

Introduction: The solitary kidney (SK) is currently debated in the literature, as living kidney donation is extensively used and the diagnosis of congenital SK is frequent. Tubulointerstitial lesions associated with adaptive phenomena may occur early within the SK., Aims: Analysis of the significance of urinary biomarkers in the assessment of tubulointerstitial lesions of the SK., Methods: A cross-sectional study of 37 patients with SK included 18 patients-acquired SK (mean age 56.44 ± 12.20 years, interval from nephrectomy 10.94 ± 9.37 years), 19 patients-congenital SK (mean age 41.52 ± 10.54 years). Urinary NAG, urinary alpha-1-microglobulin, albuminuria, eGFR (CKD-EPI equation) were measured., Results: In acquired SK, NAG increased in 60.66%, urinary alpha 1-microglobulin in 16.66%, albuminuria in 55.55% of patients. Inverse correlation with eGFR presented NAG (R(2 )= 0.537, p = 0.022), urinary alpha 1-microglobulin (R(2 )= 0.702, p = 0.001), albuminuria (R(2 )= 0.655, p = 0.003). In congenital SK, NAG increased in 52.63%, urinary alpha 1-microglobulin in 5.26%, albuminuria in 47.36% of patients. In this group, urinary biomarkers correlated inversely with eGFR: NAG (R(2 )= 0.743, p < 0.001), urinary alpha 1-microglobulin (R(2 )= 0.701, p = 0.001), albuminuria (R(2 )= 0.821, p < 0.001). Significant correlations were found between the urinary biomarkers in both groups., Conclusions: Urinary biomarkers allow a non-invasive, sensitive, early assessment of the tubular lesions of the SK. Urinary biomarkers of PT injury parallel renal function decline, thus complementing the estimation of GFR. Monitoring of PT dysfunction is mandatory in patients with SK.

CD34 cells in the interstitial infiltrates in glomerulonephritis (GN) could be the turning point between regenerative processes and interstitial fibrosis. The aim of our study was to assess the presence of CD34+ cells in the interstitial infiltrates in GN. A cross-sectional study of 33 patients with glomerulonephritis, mean age: 43.3 ±11.31 years, 20 male and 13 female, was conducted. Conventional stains, as well as immunohistochemistry for the CD34 antigen were employed on kidney biopsies. Strength of immunohistochemical reaction was assessed semi-quantitatively. Regarding the percentage of cases with CD34+ cells in the interstitial infiltrates out of 33 patients: cells of interstitial infiltrates were 27.3% positive. The percentage of cases showing CD34+ cells at the level of interstitial infiltrates was: 44.4% in FSGS, 14.3% in membranoproliferative GN, 28.6% in membranous nephropathy, 20% in mesangial proliferative GN, 0% in minimal change disease, and 50% in crescentic GN. With the exception of minimal change disease, CD34+ cells were found in the interstitial infiltrates in all histopathological forms of GN. Some of these cells were spindle-shaped fibroblast-like cells. As inflammation in the tubulointerstitial compartment either resolves or proceeds to fibrosis, aims at reversing this process will benefit from analyses of the interstitial infiltrates harboring CD34+ cells.

Introduction and Aims: The HLA-DR antigen is a HLA class II molecule involved in the presentation of antigenic peptides to the T cell receptor, thus regulating the immune response. Renal expression of the HLA-DR antigen may indicate specific sites of immunologically-mediated kidney injury in glomerulonephritis (GN). The aim of our study was to assess the presence of the HLA-DR antigen along the nephron including the extraglomerular mesangium in GN., Methods: A cross-sectional study of 22 patients with glomerulonephritis, mean age: 46.59±10.77 years, 14 male and 8 female, was conducted. Conventional stains, as well as immunohistochemistry for the HLA-DR Antigen Alpha-Chain were employed on kidney biopsies. Immunohistochemistry was assessed using a semi-quantitative score: 0-absent, 1-mild, 2-moderate, 3-intense. Statistical analysis was performed using SPSS17., Results: Four patients presented Focal and Segmental Glomerulosclerosis (FSGS), 5 patients: membranoproliferative GN, 7 patients: membranous nephropathy, 3 patients: mesangial proliferative GN, 2 patients: minimal change disease (MCD), and 1 patient: crescentic GN. Regarding the percentage of cases with HLA-DR positive cells along the nephron out of 22 patients: glomerular endothelial cells were 100% positive, intraglomerular mesangium cells were 81.8% positive, podocytes were 36.4% positive, extraglomerular mesangium cells were 31.8% positive, proximal tubule cells were 95.5% positive, distal tubule cells were 68.2% positive, interstitial capillaries were 77.3% positive, and cells of interstitial infiltrates were 27.3% positive. The percentage of cases staining positively for the HLA-DR antigen in the extraglomerular mesangium was 25% in FSGS, 60% in membranoproliferative GN, 0% in membranous nephropathy, 33.3% in mesangial proliferative GN, 100% in minimal change disease and 0% in crescentic GN., Conclusions: A prominent HLA-DR antigen distribution was found on glomerular endothelial cells, intraglomerular mesangium cells and proximal and distal tubular cells. Extraglomerular mesangium cells and podocytes stained variably for the HLA-DR antigen, as did the cells of the interstitial infiltrates. The extraglomerular mesangium which serves as a portal of entry into the intraglomerular mesangium is endowed with antigen-presenting capabilities and is a region where induction of immune reactions could take place., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Recently, chronic Aristolochia poisoning was found responsible for the aetiology of Balkan endemic nephropathy (BEN) in Croatia, Serbia, and Bosnia, and diet was the likely route of exposure to aristolochic acid (AA). BEN, often associated with an increased incidence of upper urinary tract carcinoma (UUC), also affects residents of certain rural villages in Romania. AA is a nephrotoxin and human carcinogen that forms DNA adducts after metabolic activation, which induce characteristic TP53 mutations in urothelial tumours. Here we present the first evidence linking AA exposure to UUC in residents of an endemic region in the Romanian Mehedinti County. DNA was extracted from kidney and tumour tissue of seven patients who underwent nephroureterectomy for UUC and resided in BEN villages (endemic group). Five patients with UUC from nonendemic villages served as controls. AA-DNA adducts (7-(deoxyadenosin-N(6) -yl)-aristolactam I), established biomarkers of AA exposure, were identified by (32)P-postlabelling in renal DNA of six patients from the endemic group and in one of the nonendemic group (adduct levels ranged from 0.3 to 6.5 adducts per 10(8) nucleotides). Additionally, an A to T transversion in TP53, a base substitution characteristic of AA mutagenic activity was found in urothelial tumour DNA of one patient from the endemic group. Our results provide a molecular link to the cause of urothelial tumours in BEN regions of Romania indicating that AA is the common aetiological agent for BEN across its numerous geographical foci., (Copyright © 2012 Wiley Periodicals, Inc.)

This paper draws attention to the relationship between the clinical and biological picture of SLE and the immune mechanisms of this disease. The presence, in the same patient, of erythema multiforme-like skin lesions and erythemato-squamous lesions specific for SLE together with a characteristic immune picture (speckled antinuclear antibodies (ANAs), positive anti-Ro antibodies, positive rheumatoid factor) raise the question of a relationship between the immune mechanisms in SLE and the clinical picture. A case of Rowell's syndrome is discussed: systemic lupus erythematosus diagnosed on the occasion of an erythema multiforme-like rash. Starting from this case, we analyse if the clinical and biological picture in SLE is an expression of the immune mechanisms involved in this disease. Our patient presented with speckled antinuclear antibodies, positive rheumatoid factor, anti-Ro antibodies, suggestive of Rowell's syndrome. The patient manifested rheumatoid-like articular pain and high titer rheumatoid factor. Clinically, we found erythema multiforme-like and erythemato-squamous lesions. The patient developed nephrotic syndrome (proteinuria 11.8g/24h), and renal failure (creatinine 3.08 mg/dl). The renal biopsy showed mesangial proliferative glomerulonephritis class II (ISN/RPS). Under treatment with prednisone the nephrotic syndrome evolved into remission (traces of proteinuria) and serum creatinine declined (1.03 mg/dl). The cutaneous syndrome had a spectacular evolution, too. The question is raised of the existence in Rowell's syndrome of immune mechanisms commonly encountered in SLE and a subset associated with the cutaneous erythema multiforme-like rash and pseudo-rheumatoid arthritis manifestations.

We consider that re-assessment of the vascular status is necessary, even mandatory, in patients with CKD when initiating dialysis because of two reasons:--assessment of vascular remodelling is important for establishing the artery-venous fistula as it can supply appreciative data on its success and duration;--vascular remodelling plays an important part in cardio-vascular pathology of patients dialysed, with the required consecutive prophylactic measures. In chronic kidney disease, calcium deposits at extra-skeletal level also affect the vessels, determining calcifications of both the vascular intima and media. Atherosclerosis and arteriosclerosis are present in patients with CKD and they contribute to diminishing the elasticity of the artery wall by vascular remodelling. Vascular remodelling determines thickening of the artery wall, respectively of the thickness of the arterial intima-media. Thus, arteries lose their elasticity, and the wall of the arterial tree wall turns stiff. Arterial stiffness is a process that precedes the development-proper of atherosclerosis, determined by cumulative exposure to various risk factors. Atherosclerosis is a focal process, in which indemne areas alternate with areas with atheroma plaques at intima level, and arteriosclerosis is a diffuse process located at the level of the arterial media. Non-invasive assessment of arterial stiffness can be achieved by analyzing pulse wave velocity and the augmentation index. We studied a group of 35 patients with chronic kidney insufficiency, CKD, stage 5, with an average age of 52.03 +/- 17.36 years, of whom 15 (43%) were females and 20 (57%) were males. The investigated parameters presented the following average values: PWV = 16.7 +/- 1.27 m/s; IMT = 1.63 +/- 0.18 mm; Aix = 36.14 +/- 9.98%; AAI = 0.78 +/- 0.2. The assessment of vascular stiffness in chronically dialysed patients offers better appreciation of vascular stiffness. Knowing the amplitude of the vascular remodelling process is of special importance for deciding the place and modality of performing the vascular access with regard to replacing the kidney function and to preventing cardiovascular events in dialysed patients.

The kidney is under the influence of sexual hormones. Estrogens have a favourable role in the progression of some chronic renal diseases. Estrogen hormones act upon the nephron component cells, regulating several processes going on at this level. One of the most important actions of the estrogens is represented by the protective effect on the kidneys, estrogens attenuating glomerulosclerosis and tubulo-interstitial fibrosis. Thus, estrogens have nephroprotective effects. Phosphorus-calcium metabolism disturbances during chronic kidney disease are influenced by numerous regulatory factors: parathormone, vitamin D fibroblast growth factor, 23. Estrogens play an important part in disturbances of the phosphorus-calcium metabolism, co-operating with these factors. They exert favourable effects on renal osteodystrophy, the main consequence of phosphorus-calcium disturbances. Hormonal dysfunction in chronic kidney disease is clinically accompanied by sexual dysfunction that influences the life quality of these patients. In advanced stages of chronic kidney disease, especially in dialysed patients, these sexual dysfunctions can be more evident. Hormonal replacement therapy and estrogen therapy- receptor modulating therapy have an important role in correcting hormonal dysfunctions manifest in chronic kidney disease. Caution is necessary in case of a would-be pregnancy in patients with chronic kidney disease, given its risks and the complexity of the problem. Renal transplantation corrects to a great extent hormonal dysfunctions in chronic kidney disease.

Introduction and Aims: N-Acetyl-β-D-glucosaminidase (NAG), a marker of renal tubular dysfunction, is increased in patients with lupus nephritis. In addition to the toxic effects of proteinuria, patients with lupus nephritis may exhibit other factors that contribute to tubular dysfunction, such as pathogenic antitubular basement membrane antibodies. The aim of our study was to assess urinary NAG, proteinuria, and glomerular filtration rate (GFR) before treatment and after 7 and 30 days of oral prednisone therapy in patients with lupus nephritis., Methods: Ten patients with lupus nephritis, all females, mean age: 29.4 ± 10.17 years, were enrolled into the study. All the patients received oral prednisone 1 mg/kg. Twenty healthy subjects served as controls. We measured urinary NAG before treatment and after 7 and 30 days of oral prednisone therapy. Proteinuria, GFR, blood pressure, and side effects of therapy were also followed up. Urinary NAG was measured using the colorimetrical method and expressed as units per gram of creatinine (U/gCr). Statistical analysis (Wilcoxon signed ranks test and Wilcoxon rank sum test) was performed using SPSS 17., Results: In the 10 patients with lupus nephritis, urinary NAG before treatment was 16.9 ± 13.39 U/gCr (P = 0.005 compared with controls). NAG in controls was 1.73 ± 0.51 U/gCr. Proteinuria before treatment was 3.84 ± 1.93 g/24 h. The GFR before treatment was 50.48 ± 11.98 mL/min/1.73 m². After 7 days of prednisone, urinary NAG was 23.55 ± 25.25 U/gCr (P = 0.878 compared with baseline, and P = 0.02 compared with controls). Proteinuria was 2.94 ± 1.3 g/24 h (P = 0.005 compared with baseline), and the GFR was 58.11 ± 13.64 mL/min/1.73 m² (P = 0.005 compared with baseline). After 30 days of prednisone, urinary NAG was 11.77 ± 12.18 U/gCr (P = 0.203 compared with baseline, P = 0.022 compared with the value after 7 days of prednisone, and P = 0.01 compared with controls). Proteinuria was 1.73 ± 0.68 g/24 h (P = 0.005 compared with baseline, and P = 0.005 compared with the value after 7 days of prednisone), and the GFR was 67.49 ± 16.42 mL/min/1.73 m² (P = 0.005 compared with baseline and P = 0.009 compared with the value after 7 days of prednisone). Blood pressure measurements did not show any significant changes. No major side effects of steroid therapy were noticed., Conclusions: Urinary NAG showed a significant reduction between 7 and 30 days of therapy. The reduction in urinary NAG set in later than the decline in proteinuria and the improvement in GFR. Further studies incorporating a longer follow-up are needed to observe whether the reduction in NAG persists upon continuation of prednisone therapy.

Hypertension is in 85 to 90% of cases of unknown etiology, in spite of efforts undertaken by modern medicine to elucidate it. Numerous experimental studies were conducted in order to explain the pathogeny of this disease. Recent observations revealed that during therapy with anti-VEGF medication,used in treating different forms of cancer, hypertension and proteinuria occur, and at kidney level endothelial injuries appear similar to pregnancy-related hypertension. Antiangiogenic factors, such as sFlt-1, are produced during pregnancy-induced hypertension, especially in preeclampsia. They block the circulating VEGF. Consequently, proteinuria, and sometimes oedema occur together with hypertension. Renal injuries are of glomerular endotheliosis type. It is appreciated that one can draw a parallel between these pathologic situations, as is ablative treatment of antiangiogenic medication (anti-VEGF) and pregnancy-induced hypertension, preeclampsia, respectively. Since in pregnancy-induced hypertension angiogenic factors have an important role, we analyse their implication in other types of hypertension, in myocardial infarction, and in endothelial dysfunction in the course of CKD. The main pathogenic mechanism of pregnancy-induced hypertension that causes the disease is placental ischaemia. This is followed by the placental release of pressor substances that are involved both in generalised endotheliosis that characterizes the disease, and in hypertension. The prototype hypertension caused by renal ischaemia is renal artery stenosis. Both pregnancy-induced hypertension and hypertension in renal artery stenosis have a similar factor in their pathogeny, that is organ ischaemia with production of consecutive pressor substances. Since this ischaemic factor can intervene in other forms of hypertension, its characterisation becomes of importance at present. Thus, pregnancy-induced hypertension in pregnancy can represent a real pathogenic model of hypertension that is reflected in non-pregnancy hypertension. The paper presents the particularities of pregnancy-induced hypertension, as well as its parallelism with other types of hypertension that are determined by organ ischaemia or that produce ablation of angiogenic factors.

Introduction: HBV and HCV chronic hepatitis can be accompanied by secondary renal disease. In addition, these patients receive antiviral drugs with potential nephrotoxicity. It is known that interferon (IFN) therapy in HCV-infected kidney transplant recipients is followed by rejection of the transplant in 50% of the cases. Ribavirin is contraindicated in hemodialyzed patients and in patients with a GFR <50 ml/min/1.73 m(2). IFN therapy requires dosage reduction and close monitoring in patients with a GFR <50 ml/min/1.73 m(2) and in patients with end stage renal disease. The aim of our study was to assess the nephrotoxicity of antiviral drugs in patients with chronic hepatitis by measuring three renal biomarkers: urinary albumin, N-acetyl-β-D-glucosaminidase (NAG) and α 1-microglobulin, as well as glomerular filtration rate (GFR-MDRD4) before and at 6 months of therapy., Methods: Fifty-five patients (28 male and 27 female, with a mean age of 47.85 ± 12.03 years) with chronic hepatitis (40 patients with HCV, 13 patients with HBV, 1 patient with HBV+HCV, and 1 patient with HBV+HDV) were enrolled into the study. Different antiviral drug associations were used on a case-by-case basis. The 40 patients with HCV chronic hepatitis received either Peg-IFN-α 2a+Ribavirin (37 patients) or Peg-IFN-α 2b+Ribavirin (3 patients). The 13 patients with HBV chronic hepatitis received Peg-IFN-α 2a (9 patients), Lamivudine (2 patients), Entecavir (1 patient), or Adefovir (1 patient). The patient with HBV+HCV chronic hepatitis received Peg-IFN-α 2a+Ribavirin. The patient with HBV+HDV chronic hepatitis received IFN-α 2a. Urinary albumin (ELISA), NAG (colorimetrical method), α 1-microglobulin (ELISA), and serum creatinine were measured before and at 6 months of antiviral therapy. Urinary markers were expressed as either mg/gCr (for albumin and α 1-microglobulin) or U/gCr (for NAG). Statistical analysis (Pearson's correlation coefficient, paired t-test and χ(2)-test) was performed., Results: At 6 months of therapy urinary albumin/gCr did not increase significantly: 16.58 ± 23.39 vs. 15.85 ± 24.96 mg/gCr before therapy, p = 0.87. Urinary NAG/gCr did not increase significantly: 4.21 ± 3.37 vs. 3.83 ± 3.2 U/gCr before therapy, p = 0.53. Urinary α 1-microglobulin/gCr was almost unchanged: 4.38 ± 4.47 vs. 4.38 ± 3.57 mg/gCr before therapy, p = 0.99. The GFR did not decline significantly: 92.41 ± 22.21 vs. 94.59 ± 36.1 ml/min/1.73 m(2) before therapy, p = 0.7. Ten patients (18.18%) were albuminuric before therapy, and 14 patients (25.45%) were albuminuric at 6 months of therapy, a non-significant increase (p = 0.35). We found a correlation between urinary albumin/gCr and NAG/gCr and between urinary albumin/gCr and α 1-microglobulin/gCr both at baseline and at 6 months of therapy: r = 0.54, p = 0.0005; r = 0.29, p = 0.03; r = 0.51, p = 0.0005; and r = 0.4, p = 0.002, respectively. In the patient receiving Adefovir, a known nephrotoxic drug, two of the three biomarkers (urinary albumin/gCr and NAG/gCr) increased, most notably NAG/gCr. Both HCV and HBV chronic hepatitis therapy were associated with non-significant changes in renal biomarker excretion and GFR., Conclusions: With the exception of Adefovir, all of the drug associations used in this study were safe.

We present a case of idiopathic retroperitoneal fibrosis (RPF) in a female patient of 45 years, obese (BMI = 39 kg/sqm), hypertensive since 2005, with diabetes mellitus treated with diet and diabetes insipidus in whom, during a routine control, the following has been found: serum creatinine 1.74 mg/dl, and an inflammatory syndrome associated with fever. Spiral-CT (Multi-slice-Sensation 64) scan shows retroperitoneal fibrosis in relation with periaortitis that affects the thoracic and abdominal aorta. RPF is extending perirenally and at the level of the renal hilum with subsequent calyceal dilations (hydrocalycosis) associated with left renal artery stenosis. The particularity of the case is represented by the perirenal and intrarenal evolution of fibrosis with left renal artery stenosis with moderate impairment of renal function reversible under treatment with Tamoxifen. This case, with chronic periaortitis subsequent to an extended aortic atherosclerosis with retroperitoneal fibrosis can be representative for the pathogenic relationship between atherosclerosis and fibrosis.

Diabetic nephropathy (DN) presents a complex pathogenesis in which both the vascular system and the metabolism, in its complexity and mainly glucidic metabolism, are involved. Together with the glucid metabolism, lipid metabolism, anemia, oxidative stress, generalised inflammation, vitamin D disorders and smoking participate in DN pathogenesis. All these factors that disturb the homeostasis of the patient with DN require protective factors which will be presented in the second part of the paper. Like hypotensive medication, and especially the inhibitors of the renin angiotensin aldosterone (RAAS) system, antiproteinuric medication, and especially intensive control of glycaemia that have an important protective role, the pathogenic factors mentioned above also require protective measures. As they interest the whole organism in DN and in DM, respectively, we speak about multiple organ protection or multiorgan protection. The concept of multiorgan protection is especially important in DM. Although sometimes, some measures with multiorgan protective character are applied in current practice, it is necessary that they should be gathered and applied within a well established framework, a fact that is achieved by the concept of multiorganprotection. Diabetes mellitus, requires multiple measures of protection because of its vascular and metabolic complications. Diabetic nephropathy represents an important complication of diabetes mellitus, frequently associated with its other complications. The first part of the paper presented the concept of multiorgan protection, as well as some of the main protective measures: control of blood pressure mainly by means of inhibitors of the renine angiotensine aldosterone system, glycaemia monitoring and antiproteinuric treatment. The second part of the paper refers to protective measures used in diabetes mellitus, and diabetic nephropathy, respectively, regarding control of the anaemia, of endothelial disturbances, of the metabolism of lipids, of oxidative stress, of inflammation, smoking, of the metabolism of vitamin D, respectively. Diabetic nephropathy, by the complexity of its lesions, as well as by the complications of diabetes mellitus, cannot be regarded as separate from the organism seen as a unitary whole, a reason because of which the measures of protection are not limited only to the kidney, they must address all organs and metabolism in general, requiring measures of multiorgan protection.

Introduction: Glomerular cells (mesangial, endothelial, epithelial) are activated during glomerulonephritis, a process indicated by the expression of the immunohistochemical marker α-smooth muscle actin (SMA). Many growth factors participate in the above-mentioned processes, among them of great importance is the transforming growth factor β (TGF-β). The result of these changes is represented by active lesions (mesangial matrix increase, mesangial cell proliferation) and chronic fibrotic lesions (glomerulosclerosis)., Methodology: We studied a group of 41 patients with primary and secondary glomerulonephritis (24 males, 17 females, mean age 45.5 ± 12.9 years), which underwent kidney biopsies, processed in light microscopy. We performed immunohistochemistry procedures with monoclonal antibodies (performed with the LSAB2-HRP system: anti-α-SMA, and anti-TGF-β), which were assessed using a semiquantitative score, that was correlated with the histological and biological data. In order to quantify the histological changes and to assess the extent of active-inflammatory and chronic-sclerotic/fibrotic lesions, we adapted a scoring system initially used only for lupus nephritis, and ANCA-associated vasculitis., Results: TGF-β expression in glomerular endothelial cells correlated with mesangial matrix increase (r=0.28, p<0.05), total activity index (r=0.29, p<0.05) and total chronicity index (r=0.34, p<0.05). Glomerular epithelial cell TGF-β correlates with mesangial proliferation (r=0.29, p<0.05), mesangial matrix increase (r=0.4, p<0.01) and total activity index (r=0.28, p<0.05). We observed a strong correlation between endothelial immunolabeling of SMA and the mesangial proliferation score (r=-0.96, p<0.005) and also an indirect correlation with the glomerulosclerosis score (r=-0.35, p<0.05) and the total chronicity index (r=-0.39, p<0.05). Concerning biological data there was a correlation between mesangial SMA expression and serum creatinine (r=0.60, p<0.001) and an indirect correlation with GFR (r=-0.37, p<0.05)., Conclusions: We conclude that TGF-β has a key role in determining glomerulosclerosis especially through mesangial matrix increase, but possibly also through mesangial cells proliferation. Another role of this growth factor is related to transdifferentiation, not only epithelial-mesenchymal, but also endothelial-mesenchymal.

Balkan Endemic nephropathy (BEN) is a tubulointerstitial disease of unknown etiology signaled in a limited geographical area. In the neighbourhood of endemic villages are coal deposits from the Pliocene, that contain toxic substances that by mobilizing groundwater can leach in water sources used by the inhabitants. In the present paper the possible impact of the coal from Pliocene on people that worked many years in mines in the endemic County Mehedinti, Romania, and who lived in this area are analysed. The risk of toxicity of coal was theoretically increased in miners because they consumed frequently water from mine springs that came from coal layers, while at home water from wells could have been contaminated by toxic substances from coal. It has been found that only 5 of the 96 patients with BEN were under dialysis program in 2008. Also out of 34 former miners only 3 had GFR < 60 ml/min/1.73 sqm, and only one with creatinine of 3 mg/dl had GFR < 30 ml/min/1.73 sqm. The mean GFR in the 34 miners was: 94.13 +/- 26.58 ml/min/1.73 sqm. We analysed GFR and proteinuria in persons from the endemic zone from 2 types of villages: some with mining activity presently (Husnicioara) others where presently there are no mining activities (Hinova, Bistrita, Livezile). We also analysed comparatively 2 non-endemic localities near the endemic focus: Drobeta Turnu Severin (without mining activity) and Motru with mining activity where different coal deposits are (non-Pliocene). Data were provided from the family doctors databases. The GFR was lower in the inhabitants from the endemic villages Bistrita and Hinova than in the investigated inhabitants from the non-endemic town Drobeta Turnu Severin (p = 0.008 and p = 0.0004 respectively). Inhabitants from the endemic village Husnicioara (Pliocene coal mine still functioning) had a higher GFR than inhabitants from Drobeta Turnu Severin and higher than inhabitants from the endemic village Livezile (mine closed 10 years ago): p = 0.0055 and p = 0.001 respectively, but a lower than the investigated inhabitants from the non-endemic town Motru (where a non-Pliocene coal mine is functioning): p < 0.001. Proteinuria was present in 8.03% of the inhabitants from the endemic village Bistrita and in 7.4% of the inhabitants from the endemic village Hinova. In the non-endemic town Drobeta Turnu Severin, proteinuria was present in 7.08% of the investigated inhabitants. Proteinuria was present in 0.78% of the investigated inhabitants of the non-endemic town Motru (where a non-Pliocene coal mine is functioning) and 2.5% of the inhabitants of the endemic village Husnicioara (Pliocene coal mine still functioning). Our paper does not show any relationship between exposure to Pliocene coal and the etiology of BEN.

Introduction: The aim of our study was to clarify the hypothesis that proximal tubule (PT) dysfunction may be responsible for early diabetic nephropathy (DN), independently of preceding glomerular endothelial dysfunction. The pattern of endothelial dysfunction and its potential variability was evaluated in two vascular beds, the kidney and the brain., Methods: A total of 68 normoalbuminuric type 2 diabetes mellitus (DM) patients were enrolled in a cross-sectional study and the following parameters were assessed: urinary albumin:creatinine ratio (UACR), urinary α(1)-microglobulin, urinary β(2)-microglobulin, plasma asymmetric dimethyl-arginine (ADMA), serum creatinine, glomerular filtration rate (GFR), C-reactive protein (CRP), fibrinogen, HbA(1c); pulsatility and resistance indices in the internal carotid artery and middle cerebral artery and intima-media thickness (IMT) in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test., Results: Plasma ADMA was increased in 12 patients (17.5%), urinary α(1)-microglobulin in 19 patients (27.9%) and urinary β(2)-microglobulin in 16 patients (23.5%). Cerebral hemodynamic indices correlated with plasma ADMA, CRP, fibrinogen, duration of DM, HbA(1c) and GFR. ADMA correlated with fibrinogen, CRP, HbA(1c), duration of DM and GFR. There were no correlations between ADMA and UACR, and urinary α(1)-/β(2)-microglobulin. Also, no correlations were found between urinary α(1)-/β(2)-microglobulin and UACR, HbA(1c), duration of DM and GFR., Conclusion: The increase in urinary α(1)-/β(2)-microglobulin precedes the stage of albuminuria. It may be assumed that early DN is related to PT dysfunction. Endothelial dysfunction plays a pivotal role in the brain vasculature, while its involvement in the development of early DN is not conditional on the occurrence of albuminuria., (Copyright © 2010 S. Karger AG, Basel.)

The study assesses the presence of asymptomatic urinary anomalies in patients with inflammatory bowel disease. Asymptomatic urinary anomalies are mainly due to glomerular nephritis, they being one of the forms of its manifestation, together with chronic nephrotic and nephritic syndromes. We identified urinary anomalies in 18 patients (20%) with bowel inflammatory disease that consisted of haematuria in 8 (9%) patients, isolated proteinuria in 5 (6%) patients and haematuria associated with proteinuria in 5 (6%) patients. Asymptomatic urinary anomalies were more frequent in patients with the Crohn disease than in those with ulcerative colitis. We identified RFG under 60ml/min in 4 patients with asymptomatic urinary anomalies. It is very easy to evaluate asymptomatic urinary anomalies with dipstick. This method is also required in current practice for patients with urinary anomalies for identifying the glomerular disease that might have caused them. One must take into consideration differential diagnosis with other diseases that can manifest themselves with proteinuria or isolated proteinuria. One must also take into account the fact that urinary anomalies may also be related to administration of 5-aminosalicylates.

During the last years renal abscesses are being diagnosed with increasing frequency in Nephrology departments. Progresses achieved in imaging procedures permit a timely diagnosis of renal abscesses. At the same time modern antibiotic therapies permit the treatment of this disease in Nephrology departments. In the current paper we present some specifics of renal abscess management encountered in a Nephrology department in western Romania. We performed a retrospective analysis of 2793 patients with upper urinary tract infection hospitalised during 2002-2009 in our Nephrology Department, of whom 44 showed renal abscesses. Uropathic factors were identified less frequently, in 28% of the renal abscess cases, compared to cases in the literature where these have been reported in over 50% of the patients. General predisposing conditions were pregnancy in 7%, postviral cirrhosis in 4%, diabetes mellitus in 4%, surgically single kidney in 2%, polycystic kidney disease in 4% of the patients. We diagnosed renal abscesses in relatively young patients (mean age 38.73 +/- 19.64), fact that could be due to a decreased immune resistance of these patients. Renal function impairment was present in 17% of the patients. Urine cultures were positive in 25% with a predominance of E. coli and rarely of other germs (e.g. Citrobacter and Candida albicans). Therapy consisted of broad spectrum antibiotics applied to all patients. Two patients required the insertion of double J catheter. Five patients (11%) were referred to the Urology Department, where one patient underwent nephrectomy. Renal abscess was diagnosed and treated in the majority of cases in the Nephrology Department, and only in special cases is a referral to the Urology clinic required.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephritis seen primarily in countries in the Balkan Peninsula. The disease, which was first described in Romania 50 years ago, often manifests as a form of chronic nephritis that is also associated with upper urothelial cancers (UUC). This review summarizes the observations and studies performed in Romania regarding this disease during the last 50 years with particular emphasis on Mehedinti county. The paper analyzes current data on the epidemiology of the disease in this area, specifically in relation to the observations made in dialysis centers in the same area. It also discusses the diagnostic criteria of patients with BEN stemming from collaborations between specialists working in other countries affected by the disease. Moreover, the paper analyzes the main etiological factors suspected to play a role in BEN: aristolochic acid (the disease has many similarities to aristolochic nephropathy caused by Chinese herbs), mycotoxins, toxic substances from pliocene lignite, genetic factors, and viruses. Studies performed by Romanian authors are presented briefly in comparison to studies performed by other authors. Finally, given that BEN is an important health problem in the region, the relationship between BEN and UUC is further analyzed.

The kidney may be affected in the processes of microbial, viral, parasitic infections. Knowledge of renal disease during chronic infection, with a different location than the throat, is of particular importance for the practicing physician for the detection and prevention of impaired renal function. Chronic kidney disease recovered in the early stages can prevent the progression of renal function decline. We studied a total of 85 patients with varicose ulcers with a mean age of 66.78 +/- 12.09 years, hospitalized in the Clinic of Dermatology and a control group consisting of 110 apparently healthy individuals. Urinary abnormalities have been detected in 26 (30%) of patients studied. GFR < 60 ml/min have been detected in 14 (17%) of patients studied. CRF stage II have been detected in 36 (42%) of patients studied. We detected recurrent varicose ulcer in 2 (2%) of patients studied. In two (2%) of patients during hospitalization we found a decrease in GFR by 15 and 12 ml/min, accompanied by an increase in serum creatinine from 0.7 mg % to 1 mg % in one patient and in another patient from 1.5 mg % to 2 mg %. Urinary abnormalities detected in patients with both acute and recurrent erysipelas warn about renal impairment and the need for monitoring of the renal patients with varicose ulcers.

Introduction: Because dysfunction of the B-cell compartment is thought to be important in the pathogenesis of systemic lupus erythematosus (SLE), there has been a recent focus on therapies that target humoral immunity via multiple mechanisms. The aim of this paper was to demonstrate the importance of immunomonitoring in two cases with class II lupus nephritis on steroids who presented with a flare-up of disease. After a thorough work-up for infectious triggers of disease activity, conversion to another histopathological class of lupus nephritis was suspected. Deterioration of the patients' clinical condition made kidney biopsy impossible, and as B-cell targeted therapy was considered, we decided to perform an immunophenotypic analysis and to tailor therapy to the results of the lymphocyte profile. As we incidentally found extremely low B-cell counts, any B-cell-targeted therapy was prohibited, and cyclophosphamide (Cy) was considered a viable therapeutic option., Methods: We performed flow-cytometric lymphocyte (Ly) phenotyping (CD19, CD3, CD3CD4, CD3CD8, CD56/16) on two patients with class II lupus nephritis before and after two intravenous (i.v.) Cy pulse administrations. During all this time, patients were on steroids., Results:  Both patients showed extreme B-cell lymphopenia, a marker of active SLE, which was not greatly impacted by the treatment over the follow-up period., Conclusions: As current therapies are aimed at targeting the B cell, an important component of adaptive immunity, caution must be exercised before their use. In addition, monitoring of Ly subsets is essential due to the occurrence of extreme B-cell lymphopenia.

Objectives: The pathophysiology of the single kidney is involved in the evolution toward endstage renal disease. Furthermore, most data suggest that the renal function of the donor is maintained after nephrectomy. This study sought to analyze the difference between surgically acquired single kidney and the congenital single kidney, regarding kidney function at a similar moment in time of the existence of a single kidney., Materials and Methods: Two groups were enrolled in this study. Group A consisted of 28 patients with surgically acquired single kidney, time from nephrectomy was 30.23 +/- 10.82 years; mean age, 54.42 +/- 14.99 years. Group B consisted of 20 patients with a congenital single kidney (mean age, 30.3 +/- 10.43 years). We assessed glomerular filtration rate (Modification of Diet in Renal Disease 4 Study Equation) and the presence of classic and nonclassic risk factors for chronic kidney disease., Results: The estimated glomerular filtration rate showed no statistically significant difference between the 2 groups., Conclusions: Our study did not show any influence of surgical nephrectomy on the evolution of kidney function. Kidney function in the surgically acquired single kidney was similar to the kidney function in the congenital single kidney at a comparable time interval. Our results have potential favorable implications for kidney transplant from living donors.

Balkan endemic nephropathy (BEN) is a disease found in Romania and neighboring countries in the Balkan area. In Romania, BEN is most prevalent in Mehedinti County, located in the South of Romania near the Danube River. The etiology of the disease is as yet unknown. One of the current hypotheses concerning BEN etiology is an involvement of aristolochic acid (AA). BEN bears many similarities to aristolochic nephropathy, which is developed due to the use of Chinese herbs as therapeutic remedies in slimming diets. This paper analyzes the involvement of therapeutic remedies based on AA in the BEN found in Mehedinti County, where these herbs have been traditionally used. The presence of AA in the plasma of BEN patients as well as of other subjects, including healthy relatives of these patients and other persons from the BEN-affected area, has been analyzed. No AA was detected in the plasma of the studied subjects. This proves the absence, at the current time, of an AA contribution in the analyzed subjects. Therapeutic remedies based on AA have been used in the BEN-affected area. We were not able to reveal direct relationships between these remedies and either the development of BEN in dialyzed patients or the development of urinary-tract tumors in dialyzed patients with urothelial tumors. Therapeutic remedies based on Aristolochiaclematitis may play a stimulating role in BEN with regard to its development and the development of urinary-tract tumors. There may be a relationship between BEN and cumulative previous exposure to low doses of AA due to the consumption of contaminated foodstuffs, which could add to any contributions by therapeutic remedies.

Erysipelas is an infectious disease caused by group A beta hemolytical streptococci which may produce renal lesions, most frequently glomerular disease. Renal injury although known is less studied in practice. Rarely bioptical exams have been performed, thus the problem of the relationship erysipelas glomerular disease is practically not solved. The aim of this study was a cross-sectional analysis of renal involvement produced by erysipelas in two departments where patients with erysipelas are diagnosed and treated: Dermatology and Infectious Diseases. We investigated 166 patients (86M, 80F; mean age 61.66 +/- 18.42) with erysipelas hospitalized in the Departments of Dermatology (55 patients-33%) and Infectious Diseases (111 patients-66%) during 2005-2009. The diagnosis was established on clinical and biological data. In these patients clinical and biological exam has been performed. We assessed GFR and urinalysis (hematuria and proteinuria). The control group consisted of 110 apparently healthy persons. Of the 166 patients with erysipelas we found asymptomatic urinary abnormalities in 82 (47%), isolated proteinuria in 19 (11%) patients and proteinuria associated with hematuria in 21 (13%) patients, and isolated hematuria in 38 (23%) patients. We did not find patients with nephrotic or nephritic syndrome. In the control group we found asymptomatic urinary abnormalities in 25 (23%) of the patients. A statistically significant difference was between the two groups (p < 0.01). Asymptomatic urinary abnormalities have been more frequent in patients with erysipelas from the Infectious Diseases Department compared to those from the Dermatology Department. A statistically significant difference has been found (p < 0.03). In patients with recurrent erysipelas (43 patients-26%) we found asymptomatic urinary abnormalities in 26 (54%) of the patients compared to the presence of asymptomatic urinary abnormalities in patients with acute erysipelas in 56 out of 123 (46%). Mean GFR in patients with erysipelas was of 73.94 +/- 27.79 ml/min. It was lower in patients with recurrent erysipelas, 72.13 +/- 24.74 mL/min respectively. Association of proteinuria with hematuria was more frequent in patients with recurrent erysipelas. Patients with asymptomatic urinary abnormalities during the course of erysipelas need to be closely monitored during antibiotic treatment.

Endothelial cells (ECs) are active participants of an inflammatory process in glomeruli. EC damage has been shown to play an important role in the progression of glomerulonephritis (GN). The degree of glomerular and peritubular capillary loss in models of progressive renal disease correlates with the severity of glomerulosclerosis and interstitial fibrosis. The aim of our study was to analyze the association of vWF, CD31 and CD34 immunoreactivity with the morphological indices of glomerular sclerosis, interstitial fibrosis, activity and chronicity in GN. A cross-sectional study of 22 patients with GN was conducted. Conventional stains (hematoxylin-eosin, periodic acid Schiff and Trichrome Gömöri stains) and immunohistochemistry (vWF, CD31 and CD34) were employed on kidney biopsies. Activity and chronicity of GN, as well as glomerular segmental sclerosis and interstitial fibrosis, were evaluated according to a scoring system initially used for lupus nephritis and antineutrophil-cytoplasmic-antibody-associated vasculitis. Immunohistochemistry was assessed using a semi-quantitative score. Statistical analysis was performed using EpiInfo 6.04. The mean patient age was 46.68+/-14.09; 14 patients were male, and eight were female. Performing Spearman's rank correlation test, no correlation was found between each marker and glomerular segmental sclerosis, interstitial fibrosis, activity and chronicity, which suggests a loss of these markers and microvasculature involvement.

The paper presents data regarding the compartmentalization of the nephron related to immune processes taking place at this level. The morphofunctional compartments of the nephron (glomerular, tubulo-interstitial and juxtaglomerular) become immune compartments during immune processes. The paper shows the immune cells located in the morphofunctional compartments of the nephron and the relationship between them. It is considered that the presence of immune cells in these compartments is a dynamic process; the number of infiltrating cells is reduced under physiological conditions and increases during pathological immune processes. The paper presents also the resident cells of the nephron and their immune capabilities. It also presents the professional immune cells originating in the bone marrow, which are involved in immune processes. The complex relationship between these cells by means of the cytokine network, chemokines as well as other mediators, as well as the role of immune receptors, mainly Toll-like receptors is outlined. During an immune aggression immune aggregates defined as tertiary lymphoid organs are formed at the level of the nephron. These lymphoid follicle-like structures might represent an intrarenal immune system. The compartmentalization of the nephron is part of the recently described concept of compartmentalization of the immune system.

Background: Thiazolidinediones represent a novel class of drugs that exert pleiotropic effects at various levels and lower blood glucose through reduction of insulin resistance in patients with type 2 diabetes mellitus., Main Purpose: The nephro- and neuroprotective effects of rosiglitazone vs. glimepiride were evaluated in normoalbuminuric patients with type 2 diabetes mellitus. The relevance of several biomarkers in the diagnosis of incipient diabetic nephropathy and cerebral microangiopathy was also assessed., Methods: A total of 34 normoalbuminuric patients with type 2 diabetes mellitus were enrolled in a 1-year open-label randomized controlled trial. Group A comprised 17 patients (7 men, 10 women, mean age 63 +/- 8.07 years) treated with rosiglitazone plus metformin; Group B comprised 17 patients (7 men, 10 women, mean age 63.2 +/- 7.19 years) treated with glimepiride plus metformin. All patients were assessed at initiation, at 6 months and by the end of the study concerning serum and urinary beta2-microglobulin, urinary a1-microglobulin, serum cystatin C, serum creatinine, glomerular filtration rate, C-reactive protein, fibrinogen, glycated hemoglobin, cholesterol, triglycerides, hemoglobin, and the urinary albumin/creatinine ratio (UACR). Cerebral hemodynamic parameters were also measured: pulsatility index and resistance index in the internal carotid artery and middle cerebral artery, and intima-media thickness in the common carotid artery., Results: At 1 year there were differences between groups A and B regarding serum cystatin C (P < 0.04), urinary beta2-microglobulin (P < 0.004), urinary a1-microglobulin (P < 0.0001), C-reactive protein (P < 0.0001), fibrinogen (P < 0.0001), serum creatinine (P < 0.0024), glomerular filtration rate (P < 0.0010), UACR (P < 0.0001), and the cerebral hemodynamic indices. The increase in a1- and beta2-microglobulin preceded the occurrence of microalbuminuria. UACR correlated with urinary a1- microglobulin (r = 0.4854), urinary beta2-microglobulin (r = 0.4867), and serum cystatin C (r = 0.3702). The cerebrovascular parameters improved in group A vs. group B and correlated with urinary beta2- and a1-microglobulin, C-reactive protein, fibrinogen, glomerular filtration rate, and duration of diabetes., Conclusion: Rosiglitazone demonstrated its nephro- and neuroprotective effects in normoalbuminuric patients with type 2 diabetes mellitus by the end of the follow-up period and these effects were beyond glycemic control. Urinary beta2- and a1-microglobulin are significant biomarkers for incipient diabetic nephropathy and diabetic cerebral microangiopathy. These biomarkers showed that proximal tubule dysfunction may develop before the stage of microalbuminuria.

CD34, traditionally a marker of hematopoietic stem cells (HSCs), was found on endothelial cells and fibroblasts as well. At the level of the extraglomerular or intraglomerular mesangium, CD34 may signal either the presence of HSCs or, conversely, may be a marker of transdifferentiation. CD34-positive cells of the extraglomerular mesangium could migrate into the intraglomerular mesangium and participate in reparative processes at this level. The aim of our study was to analyze the presence of CD34 at the level of the extraglomerular and intraglomerular mesangium and its relationship with histological markers of activity and chronicity, as well as with other immunohistochemical markers in glomerulonephritis (GN). A cross-sectional study of 36 patients with GN was conducted. Conventional stains: hematoxylin-eosin, periodic acid Schiff, and Trichrome Gömöri, as well as immunohistochemistry: CD34, alpha smooth muscle actin (alpha SMA), vimentin, and proliferating cell nuclear antigen (PCNA) were employed. Activity and chronicity of GN were evaluated according to a scoring system initially used for lupus nephritis and antineutrophil-cytoplasmic-antibody-associated vasculitis. Immunohistochemistry was assessed using a semiquantitative score. The mean age was 46.44 +/- 12.97 years; 22 were male and 14 were female. The extraglomerular mesangium was visible on specimens in 30 patients. CD34 was present in the extraglomerular mesangium in 15 patients: 11 of these patients showed concomitant intraglomerular and extraglomerular mesangial CD34 immunostaining, while four showed only extraglomerular mesangial immunostaining. In three patients, CD34 immunostaining was present only in the intraglomerular mesangium. Twelve patients showed negative immunostaining in both the extraglomerular and the intraglomerular mesangium. Overall, there was a fair degree of relationship, which did not reach statistical significance between CD34 in the extraglomerular mesangium and CD34 in the intraglomerular mesangium across the 36 patients. In the intraglomerular mesangium, CD34 did not significantly correlate with mesangial alpha SMA, vimentin, PCNA, and activity or chronicity index. In the extraglomerular mesangium, CD34 did not show a significant correlation with alpha SMA, vimentin, or PCNA. The activity index and the chronicity index showed a good correlation with serum creatinine. Mesangial cell proliferation correlated well with the mesangial matrix increase, while interstitial vimentin showed a good correlation with interstitial alpha SMA. We demonstrated the presence of CD34 in the extraglomerular mesangium, which could be related to transdifferentiated mesangial cells or to HSCs in the absence of blood vessels at this level. Our study shows the value of histological indices for evaluating GN but cannot assign significance to CD34 immunolabeling for the assessment of GN.

The aim of this study was to determine the relationship between histological, immunohistochemical (IHC) and biological data in the assessment of interstitial fibrosis in patients with glomerular diseases. A group of 41 patients with primary and secondary glomerulonephritis was studied. In order to quantify the histological changes and to assess the extent of active-inflammatory and chronic-sclerotic/fibrotic interstitial lesions, we adapted a scoring system, initially used for lupus nephritis, and ANCA-associated vasculitis. IHC labeling procedures with monoclonal antibodies anti-smooth muscle actin (SMA), anti-vimentin and anti-transforming growth factor beta (TGFbeta) were assessed using a semi-quantitative score, correlated with the histological and biological data. Our results showed that interstitial labeling of SMA correlated with scores for sclerotic/fibrotic lesions (chronicity index) and with active-inflammatory lesions (interstitial infiltrate, activity index). Interstitial vimentin correlated with the score for interstitial infiltrate. Both interstitial vimentin and TGFbeta immunopositivity correlated with sclerotic/fibrotic lesions (interstitial fibrosis, tubular atrophies, vascular hyalinosis/fibrosis, chronicity index), and negatively with glomerular filtration rate. An important correlation was found between the interstitial labeling of the two IHC markers of myofibroblasts (SMA and vimentin). We conclude that IHC studies related to clinico-biological and histological data can have an important role in the evaluation of the glomerular diseases, but the classical histological investigation assessed through quantification has still not lost its importance.

Steroids are still the mainstay of therapy in primary chronic glomerulonephritis (PCGN), regardless of underlying disturbance or pathology. Moreover, relationship between known abnormalities and disease manifestation is stochastic, therefore treatment continues to be empirical. It is not known whether responsiveness is related to immune phenotype. We performed flowcytometric lymphocyte (Ly) phenotyping (CD19, CD3, CD3CD4, CD3CD8, CD56/16) on 16 patients (pts) (12M, 4F), mean age 37.6+/-13 years with primary chronic glomerulonephritis (PCGN): minimal change disease (MCD)--6 pts, focal and segmental glomerulosclerosis (FSGS)--4 pts, mesangial proliferative glomerulonephritis--5 pts, mesangiocapillary glomerulonephritis--1 pt, before and at 7 days of oral Prednisone 1 mg/kg/day (in 2 divided doses). Before steroids: 4/16 pts(25%) had elevated BP; 9/16(56.2) showed nephrotic proteinuria. Serum creatinine was >1.2 mg% in 6/16(37.5%). At 7 days WBC count increased (13,079.37+/-4966.4/microl vs. 8021.25+/-2077.4/microl; p=0.0007), Ly percentage (%) decreased (20.30+/-9% vs. 29.9+/-10.4%; p=0.0095), while absolute (abs.) Ly count remained unchanged. Both CD19 Ly% and CD19 Ly abs. count increased (16.13+/-6.5% vs. 9.52+/-3.7%; p=0.0015, and 410.012+/-29.7/microl vs. 223.56+/-123.8/microl; p=0.0077, respectively). NK (natural killer)% decreased (9.15+/-5.2% vs. 14.19+/-7.1%; p=0.0296). CD3, CD3CD4, CD3CD8 Ly subsets and CD4/CD8 ratio showed no change. Variation in proteinuria (2.88+/-2.1 g/24 h vs. 3.45+/-1.7 g/24 h; p=0.4) did not reach statistical significance (Wilcoxon-Mann-Whitney). In 11 pts we performed an additional analysis at 1 month. Compared to levels before steroids, there was an increase in WBC, CD19 Ly% and CD19 Ly abs. count and a decrease in NK% and NK abs. count. Other Ly subsets and CD4/CD8 ratio remained unchanged. Variation in clinical parameters (proteinuria, serum Creatinine, BP) did not reach statistical significance. Changes in Ly profile precede changes in clinical parameters and thus are divergent. While our patients proved to be early non-responders, further studies to elucidate whether profile changes provide for response specification are warranted.

Background: Cerebrovascular reactivity (CVR) is a hemodynamic parameter representing the increase in normal cerebral artery blood flow in response to a vasodilatory stimulus such as hypercapnia., Main Purpose: The aim of the study was to assess CVR using transcranial Doppler ultrasound and the breath-holding test (BHT) in normotensive patients with non-insulin-dependent diabetes mellitus (NIDDM). The cerebrovascular response to hypercapnia was evaluated in relation to risk factors for cerebral microangiopathy., Methods: The study was carried out in a group of 34 normotensive NIDDM patients and a group of 31 sex- and age-matched normal controls. The NIDDM group was subdivided into 21 patients with microangiopathic complications (Group A, 12 men, 9 women; mean age 58.77 +/- 8.91 years) and 13 patients with no such complications (Group B, 8 men, 5 women; mean age 56.34 +/- 9.83 years). The control group comprised 17 men and 14 women (Group C, mean age 58.43 +/- 6.31 years). Exclusion criteria were hypertension and past or present symptomatic cerebrovascular disease. The BHT consisted of spontaneous hypercapnia induced by holding the breath for 20 seconds. CVR was estimated in relation to the increase in the mean flow velocity (MFV) compared with the basal velocity in both middle cerebral arteries during hypercapnia., Results: In Group A, the CVR was significantly decreased in 71.42% of patients, whereas in Group B only 30.76% of patients presented with mildly to moderately impaired CVR. Predictors for impaired % increase in the MFV during the BHT demonstrated by univariate regression analysis were: duration of diabetes (r = 0.802; P < 0.0001), fibrinogen (r = 0.574; P < 0.0001), C-reactive protein (r = 0.525; P < 0.001), proteinuria (r = 0.924; P < 0.0001) and serum creatinine (r = 0.969; P < 0.0001). Multivariate regression analysis showed as predictors: duration of diabetes (P < 0.0001), proteinuria (P < 0.0001) and serum creatinine (P < 0.0001)., Conclusion: CVR is impaired in normotensive NIDDM patients. These cerebral hemodynamic changes correlate significantly with the duration of DM, parameters of inflammation, proteinuria and serum creatinine.

Background: Epidemiological data of renal disease are available from large national renal biopsy registries from Central and Western European countries; in contrast, detailed epidemiological data from Eastern European countries are missing. This report is the first review of histological data, over a period of 10 years (1995-2004), covering a population of over 6 million inhabitants and two distinct regions from an East European country - Romania., Methods: 635 eco-guided kidney biopsies from the Moldova (North-Eastern Romania, 8 counties, 4 754 048 inhabitants) and Banat (Western Romania, 3 counties, 1 454 747 inhabitants) regions were analysed. Data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, clinical diagnosis, histological diagnosis and complications after renal biopsy were collected., Results: The number of biopsies performed varied between 10.9 p.m.p./year in 1995 and 11.3 p.m.p./year in 2004. The most common clinical syndromes - as indication for performing the renal biopsy - were: nephrotic syndrome (52.3%), followed by nephritic syndrome (21.9%), acute renal failure (ARF) (12.4%), chronic kidney disease (CKD) (10.2%) and asymptomatic urinary abnormalities (AUA) (3.3% of the cases). The major histological groups identified were: primary glomerulonephritis (GN) (66.2%), secondary GN (26.4%), vascular nephropathies (2.3%), and tubulointerstitial nephropathies (TIN) (1.5%) of the cases. Among primary GN's, the most frequent diagnoses were: membranoproliferative GN (MPGN) (29.4%, incidence in 2004 - 9.3 p.m.p./year), mesangioproliferative GN (MesGN) (28.9%, incidence - 10 p.m.p./year), membranous GN (MGN) (11.2%, incidence - 5.3 p.m.p./year), minimal change disease (MCD) (8.5%, incidence - 7.3 p.m.p./year), focal and segmental glomerulosclerosis (FSGS) (11.5%, incidence - 3.3 p.m.p./year) and crescentic GN (CGN) (7.9%, incidence - 3.3 p.m.p./year). The prevalence of membranoproliferative GN significantly decreased from 1995 to 2004. The prevalence of different types of secondary GN was similar to Western and Central European countries, with the particular difference of higher infectious diseases associated GN., Conclusion: The present data are an important contribution to the epidemiology of renal diseases in Europe, highlighting not only numerous similarities but also significant epidemiological differences in Western and Central European countries, particularly a higher, albeit declining, incidence and prevalence of membranoproliferative GN. This report represents the basis for the future of Romanian Registry of Renal Biopsies and is intended to serve as a source of information for nephrologists concerned with East European renal pathology.