Has the diversity of clinical and biological manifestations of systemic lupus erythematosus a correspondent in the diversity of immune mechanisms? Observations based on a Rowell's syndrome case associated with arthritis and nephritis.

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.

Histological changes and immunohistochemical markers in the assessment of glomerulosclerosis in patients with glomerulonephritis.

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 ß (TGF-ß). 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-ß), 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-ß 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-ß 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-ß 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.

Epidemiological data regarding Balkan endemic nephropathy in relationship with the Pliocene coal etiological hypothesis.

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.

Specifics of the renal abscess in nephrology: observations of a clinic from a county hospital in Western Romania.

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.

Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus.

AIM: The renal and cerebral protective effects of pioglitazone were assessed in normoalbuminuric patients with type 2 diabetes mellitus (DM). METHODS: A total of 68 normoalbuminuric type 2 DM patients were enrolled in a one-year open-label randomized controlled trial: 34 patients (pioglitazone-metformin) vs. 34 patients (glimepiride-metformin). All patients were assessed concerning urinary albumin: creatinine ratio (UACR), urinary alpha1-microglobulin, urinary beta2-microglobulin, plasma asymmetric dymethyl-arginine (ADMA), GFR, hsC-reactive protein, fibrinogen, HbA1c; pulsatility index, resistance index in the internal carotid artery and middle cerebral artery, intima-media thickness in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test. RESULTS: At 1 year there were differences between groups regarding ADMA, urinary beta2-microglobulin, urinary alpha1-microglobulin, parameters of inflammation, serum creatinine, GFR, UACR, the cerebral haemodynamic indices. Significant correlations were found between alpha 1-microglobulin-UACR (R(2)=0.143; P=0.001) and GFR (R(2)=0.081; P=0.01); beta2-microglobulin-UACR (R(2)=0.241; P=0.0001) and GFR (R(2)=0.064; P=0.036); ADMA-GFR (R(2)=0.338; P=0.0001), parameters of inflammation, HbA1c, duration of DM, cerebral indices. There were no correlations between ADMA-UACR, urinary alpha1-microglobulin and beta2-microglobulin. CONCLUSION: Proximal tubule (PT) dysfunction precedes albuminuria and is dissociated from endothelial dysfunction in patients with type 2 DM. Pioglitazone delays PT dysfunction and improves cerebral vessels endothelial dysfunction in normoalbuminuric patients with type 2 DM.

Asymptomatic urinary anomalies, hematuria and proteinuria, in patients with inflammatory bowel disease. Preliminary study.

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.

Immune compartments of the nephron in relation to the immune system.

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.

Elements of renal injury in patients with erysipelas.

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.

Multi-organ protection and the kidney. From nephroprotection, cardioprotection, neuroprotection to multi-organ protection

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