Modulation of luminal L-alanine transport in proximal tubular cells of frog kidney induced by low micromolar Cd2+ concentration.

The kidneys are recognized as a major target of cadmium-induced toxicity. However, all mechanisms that are involved in the early stages of cadmium nephrotoxicity, particularly considering low micromolar concentrations of cadmium ions (Cd2+) are still unknown. Therefore, the aim of this study was to investigate the effects of peritubular acute exposure to micromolar Cd2+ concentration (2.3 µmol/L) on the rapid depolarization and the rate of slow repolarization of peritubular membrane potential difference (PD), induced by luminal application of L-alanine in proximal tubular cells of frog kidney. The results showed that the luminal application of L-alanine rapidly depolarized the peritubular membrane PD of -42.00 ±â€¯11.68 mV by 23.89 ±â€¯4.15 mV with an average rate of slow repolarization of 5.64 ±â€¯0.81 mV/min. Additionally, peritubular acute exposure to Cd2+ induced change in rapid depolarization of peritubular membrane PD of -53.33 ±â€¯13.01 mV by 18.78 ±â€¯3.31 mV (P < 0.01) after luminal application of L-alanine. Also, peritubular acute exposure to Cd2+ led to statistically significant decrease in the rate of slow repolarization of peritubular membrane PD (3.53 ±â€¯0.35 mV/min; P < 0.05). In conclusion, these results suggest that peritubular acute exposure to low micromolar Cd2+ concentration decreased the rapid depolarization and the rate of slow repolarization of peritubular membrane PD induced by luminal application of L-alanine. This is followed by reduced luminal sodium-coupled transport of L-alanine and this change may be one of the possible mechanisms involved in the early stages of Cd2+-induced nephrotoxicity.

Treatment of lupus nephritis by mycophenolate mofetil.

BACKGROUND/AIMS: Mycophenolate mofetil (MMF) has been increasingly used for the treatment of lupus nephritis (LN). The aim of this study was to examine the efficacy and safety of MMF used with low doses of corticosteroids as maintenance therapy in patients with LN. METHODS: The study covered 35 patients, most of them with proliferative types of LN (5 WHO class III, 26 class IV), while 1 had class V and 3 class VI nephritis. MMF was administered in the dose of 1.5-2 g/24 h and prednisone at 10-20 mg/day. The treatment effects were followed over a 12-month period. RESULTS: After 3 months of therapy significant reduction in proteinuria was achieved (2.1 +/- 2.4 g/24 h vs. 1.0 +/- 1.0 g/24 h, p < 0.01) and maintained to the end of the study. In parallel, a significant rise in serum albumin, a fall of cholesterol and a significant increase in mean glomerular filtration rate were noted. Complete remission was achieved in 16 patients (45.7%), including all patients in class III and V plus 10 patients in class IV. Not a single adverse effect was observed. CONCLUSION: MMF combined with low doses of steroids is an effective and safe treatment for the maintenance of stable remission of LN.

Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study.

BACKGROUND/AIMS: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. METHODS: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. RESULTS: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9-8.4) to 1.28 g/day (IQR 0.5-2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13-6.48) to 0.84 (IQR 0.42-2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 +/- 3.46 to 2.16 +/- 2.46, between the first (visits 1-2) and last (vists 4-5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 +/- 31.8 to 65.3 +/- 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. CONCLUSION: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

[Polycystic kidney disease--autopsy review from the period 1987-2007].

INTRODUCTION: Polycystic kidney disease is an inherited kidney disease that affects both kidneys and it is characterized by diffuse replacement of renal parenchyma by thousands of microcysts. In time, renal insufficiency develops. There are two forms of PKD: ADPKD, which is detected in adults (children are rarely affected), and ARPK, which is detected in neonates (later presentations do occur, but rarely). OBJECTIVE: The aim of this study was to analyse frequency of polycystic kidney disease, clinical data and morphological characteristics. METHOD: At the Institute of Pathology, School of Medicine, Belgrade, there were detected 33 cases of ADPKD and 20 cases of ARPKD between 1987 and 2007. RESULTS: There were no differences between incidence of ADPKD in males and females. Average age of patients with ADPKD was 52 years. In 20 (66.7%) cases of ADPKD there were neither extrarenal cysts nor extrarenal manifestations detected. In other 13 cases, we detected extrarenal cysts: hepatic cysts in 8 cases, pancreatic cysts in 5 cases. In two cases, hepatic cysts were associated with intracranial (arachnoid cysts) and extracranial aneurysms. The most frequent cause of death in patients with ADPKD was end-stage disease. ARPKD affects more often male children compared to female. 70% of children with ARPKD were male. The mean age of patients with ARPKD was 1 month. 5 patients (40%) had hepatic fibrosis. The most frequent cause of death was respiratory insufficiency (75%). In 25% of patients, the cause of death was sepsis and renal insufficiency. CONCLUSION: Morphological and clinical manifestations of the analysed cases of both types of PKD are fairly consistent with literature data. Better knowing of aethiopathogenesis of PKD will facilitate early diagnosis, based on clinical and morphological characteristics and better management of the disease.

[The significance of angiotensin-converting enzyme inhibitors genotype for ACEi response in patients with chronic allograft nephropathy].

Investigations conducted in medical centers worldwide and ours indicate that patients with chronic allograft nephropathy (CAN) will have short kidney graft survival when proteinuria and/or azotemia develop early, during the first post transplantation year. The analysis of published results suggests that angiotensin-converting enzyme (ACE) DD genotype represents unfavorable marker of rapid progression of chronic renal allograft dysfunction (CRAD). Differences of response to ACEi therapy in patients with chronic nephropathy of one's one or transplanted kidney could be explained by ACE genotype variety, where ACE DD is unfavorable genotype. Related factors influencing the ACEi therapy success in patients with particular ACE genotype are highly salt diet, interactions of genotype variety of all renin-angiotensin-aldosterone system (RAS) molecules, i.e. diversity in the ACE, angiotensinogen, AT1 receptor or aldosterone genotype, as well as differences of ACEi responses in patients with glomerular and tubulointerstitial kidney diseases. Retardation of chronic renal failure in patients with ACE DD genotype who developed chronic allograft nephropathy has been obtained with long-term ACEi treatment and restricted salt intake to 50 mmol Na+ per day. We consider that genotype investigation of RAS molecule, primarily of ACE genotype in recipient and kidney donor should be done before high-risk kidney transplantation.

[The significance of angiotensin converting enzyme inhibitors in therapy in chronic allograft nephropathy].

Angiotensin II plays a crucial role in pathologic processes of chronic allograft nephropathy (CAN) leading to chronic and progressive renal allograft dysfunction (CRAD). Systemic and glomerular hypertensions together with proteinuria occur in CAN under conditions of JGA hypertrophy with up-regulated RAS activity in the renal allograft, and they represent independent factors of rapid progression of chronic renal allograft failure. ACEi are safe and efficient antihypertensives with renoprotective effects in patients with CAN. Favorable response to ACEi has been reflected in diminished proteinuria, slow increase of creatininemia, regulation of arterial hypertension and better long-term survival of patients and kidney allografts. Our pilot study highlights the importance of ACEi therapy in CAN after renal transplantation from elder donors (>55 years).

[HIV infection and the kidneys (Part II): Morphologic changes and their diagnostic significance].

HIV-infected patients may be faced with a variety of renal problem patterns. HIV-associated nephropathy is a unique pattern of sclerosing glomerulopathy and represents the most rapidly progressive form of focal segmental glomerulosclerosis. This study involved the examination of 32 renal biopsies: by light, immunofluorescence, and electron microscopy, in order to determine the most accurate and reliable diagnostic procedure. The findings show that the most sensitive and accurate procedure is electron microscopy, capable of detecting specific EM changes very early on, which is sufficient for the diagnosis of HIV-associated nephropathy.

[Adhesion molecules in Wilm's tumor: expression and significance of beta-catenin (part II)]. / Adhezioni molekuli u Wilms-ovom tumoru: ekspresija i znacaj beta-katenina (II deo).

Beta-catenin is a glicoprotein which has an important role in cell-cell adhesion, as well as in cell signal transmission, in u regulation of gen expression and in interaction with axin and APC (adenomatous poliposis coli). Its oncogenic role in several types of carcinomas in human population is well known. It is very likely that beta-catenin as an protooncogen plays an important role in genesis of Wilms tumor. It is well known that in 15% Wilms tumors there are beta-catenin mutations, which indicates that there is a disorder in Wnt signal path that plays an important role in Wilms tumor genesis. The aim of our study was to investigate b-catenin expression in Wilms tumor, to compare it with the expression in normal renal tissue as well as to see if there is a positive correlation between b-catenin expression in Wilms tumor with tumor stage, histologic type and/or prognostic group.