Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus

Aim

Our study aimed to examine the prevalence of non-diabetic renal disease in selected patients with type 2 diabetes mellitus and to determine important risk factors for non-diabetic renal disease.

Methods

We conducted retrospective analysis of clinical, laboratory and pathohistological data of type 2 diabetes mellitus patients in whom renal biopsies were performed from January 2004 to February 2013 at Dubrava University Hospital Zagreb Croatia (n = 80).

Results

According to renal biopsy findings, isolated diabetic nephropathy was found in 46.25%, non-diabetic renal disease superimposed on diabetic nephropathy in 17.5% and isolated non-diabetic renal disease in 36.25% of the patients. The most common non-diabetic renal diseases found were: membranous nephropathy, followed by IgA nephropathy and focal segmental glomerulosclerosis. In univariate analysis shorter duration of diabetes, independence of insulin therapy, lower levels of HbA1c and absence of diabetic retinopathy were found to be significant clinical predictors of non-diabetic renal disease. In multivariate analysis only independence of insulin therapy (OR 4.418, 95%CI = 1.477–13.216) and absence of diabetic retinopathy (OR 5.579, 95%CI = 1.788–17.404) were independent predictors of non-diabetic renal disease.

Conclusions

This study confirmed usefulness of renal biopsy in patients with type 2 diabetes mellitus, due to the high prevalence of non-diabetic renal disease found. Since non-diabetic renal disease are potentially curable, we should consider renal biopsy in selected type 2 diabetes mellitus patients with renal involvement, especially in those with absence of diabetic retinopathy and independence of insulin therapy.     

Effects of Passive Stretching on the Biochemical and Biomechanical Properties of Calcaneal Tendon of Rats

The role of physical activity in affecting the composition of extracellular matrix and mechanical properties of tendons has been well studied, but little is known about the role of passive stretching. The purpose of this study was to test the hypothesis that stimulation by passive stretching may change the composition and mechanical properties of tendons. Three-month-old Wistar rats were divided into three groups: the control, animals were not submitted to stretching procedures; groups that had their calcaneal tendons manually stretched three or five times a week, for 21 days. Afterward, the calcaneal tendons were removed and assayed for hydroxyproline content and biomechanical test. The hydroxyproline content in the stretched groups was higher, suggesting that more collagen was present in the tendons of these groups. These tendons also showed higher values of maximum stress and modulus of elasticity or Young's modulus. These results indicate that stretching leads to alterations in the synthesis of the extracellular matrix components and in the mechanical properties of tendons.     

Epidemiologic data of adult native biopsy-proven renal diseases in Croatia

Purpose

There is a paucity of epidemiological data on biopsy-proven renal disease in Croatia. The purpose of this report is a review of clinical and histological data, over a period of 15 years, from the single biggest adult native renal biopsy center in Croatia.

Methods

This report includes data from 922 adult native renal biopsies in patients referred from the whole country and performed in our center from 1996 till February 2012. Data on age, gender, serum creatinine, urine sediment, 24-h proteinuria, clinical syndrome and histological diagnosis were collected and analyzed retrospectively. In all patients, light, immunofluorescence and electron microscopic analysis was performed.

Results

The median age of the patients was 48 years (interquartile range 36–59 years), and the majority of patients were men (57.8 %). The most common indication for renal biopsy was nephrotic syndrome (40.3 %) followed by asymptomatic urinary abnormalities (31.7 %). The most common biopsy-proven renal disease in total was IgA glomerulonephritis (19.3 %), followed by focal segmental glomerulosclerosis (FSGS) (15.8 %) and membranous glomerulonephritis (9.2 %). In men, similar results were found, while in women, the most common were hereditary nephritis (13.4 %), FSGS (12.9 %) and connective tissue disease–related glomerular disorders (11.6 %).

Conclusion

The presented data are an important contribution to the better understanding of the epidemiology of biopsy-proven renal disease in Croatia and Europe throughout comparison with other registry data. This data should be the basis for the formation of Croatian Registry of Renal Biopsies.     

Immune reactivity of renal transplant recipients receiving interleukin-2 receptor antagonists during the early posttransplant period

Purpose

There is a need for methods that would enable monitoring of the effects of immunosuppression on the recipient’s immune system to avoid rejection, immunodeficiency-related complications and non-immune toxicities of the drugs used in therapy.

Methods

This prospective trial included thirty patients who underwent renal transplantation in our center. All patients received an interleukin-2 receptor (IL-2R) antagonist in combination with mycophenolate, corticosteroid and calcineurin inhibitor. During the first 6 weeks after transplantation, the anti-CD3-stimulated proliferative response of peripheral blood T lymphocytes (PBTL) was studied by cell cycle analysis. The proportion of PBTL in different phases of the cell cycle and expression of IL-2R were determined by flow cytometry.

Results

As an effect of quadruple immunosuppressive therapy including IL-2R antagonists, cell cycle analysis showed an incremental decrease in the proliferative response of PBTL during the first 6 weeks after renal transplantation. A sudden drop in the proportion of IL-2R-positive cells was observed immediately after the first dose of the IL-2R antagonist and a significant antiproliferative effect on PBTL after the second dose. In vitro, IL-2R antagonists showed a dose-dependent inhibition of the anti-CD3-stimulated proliferation of PBTL of healthy blood donors.

Conclusions

Cell cycle analysis of the immune reactivity of renal allograft recipients may represent a valuable tool for the immunological posttransplant follow-up and optimization of the immunosuppressive therapy.     

Hypereosinophilic syndrome—a rare adverse event of anti-cytokine treatment in rheumatoid arthritis resolved after Janus kinase inhibitor therapy

Clinical Rheumatology - Eosinophilia is uncommon in early rheumatoid arthritis (RA). The most frequent causes of hypereosinophilia during RA treatment are atopic eczema, allergy, helminth...     

Cytotoxicity of doxorubicin‐loaded Con A‐liposomes

The present study investigated the potential of Concanavalin A lectin (Con A) conjugated to liposomes (Con A‐liposomes) for targeting doxorubicin (DOX) to cells. The physicochemical properties and the cytotoxicity of DOX‐loaded Con A‐liposomes were evaluated. DOX‐loaded Con A‐liposomes were prepared by incubation of DOX‐loaded liposomes with a Con A‐SATA derivative. Lectin biological activity was monitored before and after conjugation by a hemagglutinating assay. The cytotoxicity of DOX‐loaded Con A‐liposomes was evaluated in terms of the inhibition of NCI‐H299 and HEp‐2 cell proliferation using the MTT method. The affinity of lectinized liposomes with these cells was thus assessed by evaluating the cytotoxic effect of the DOX released into cells. Stable DOX‐loaded Con A‐liposomes were obtained and their high affinity for cells was corroborated. The encapsulation of DOX into Con A‐liposomes produced an inhibition of roughly 70% of Hep‐2 cell proliferation and 50% of cell inhibition was verified on HCI‐H292. DOX in solution was able to inhibit only 20% of cell proliferation for both cell lines. Unloaded Con A‐liposomes were not cytotoxic. The encapsulation of DOX into Con A‐liposomes improves drug penetration into cells, thereby enhancing its cytotoxicity, especially in Hep‐2 cells. Drug Dev. Res. 67:430–437, 2006. © 2006 Wiley‐Liss, Inc.     

Labeled Lectin Studies of Renal Tubular Dysgenesis and Renal Tubular Atrophy of Postnatal Renal Ischemia and end-Stage Kidney Disease

Renal tubular dysgenesis (RTD), with hypoplasia especially of renal proximal convoluted tubules and clinical neonatal anuria or oliguria, has been reported as a congenital familial (autosomal recessive) disease, variably with features of oligohydramnios, Potter syndrome, or pulmonary hypoplasia. A similar tubular lesion due to antenatal tubular atrophy has been reported for conjoined twins with twin-twin transfusion syndrome or acardia and in infants of mothers given antihypertensive agents, including angiotensin-converting enzyme (ACE) inhibitors, during pregnancy, and it has been seen as a unilateral lesion in young infants with renal artery stenosis due to arteritis or medial arterial calcinosis. The renal tubular changes in RTD are very like those of the “endocrine kidney” in experimental animals and resemble those of the renal tubular atrophy of end-stage kidney diseases such as glomerulonephritis, tubulointerstitial kidney disease, obstructive uropathy/pyelonephritis, graft rejection of transplanted kidneys, or the renal parenchymal changes seen with protracted dialysis therapy. Labeled lectins that differentially mark proximal convoluted, distal convoluted and connecting, and collecting tubules showed no distinctive differences in stainingpatterns of the hypoplastic renal tubules of infants and children with RTD, postnatal renal artery obstruction, or the various types of end-stage renal disease with the lectins used (PNA, GSL1, UEA, and LTA). The findings suggest that the renal tubular changes in some if not all the conditions studied are the result of renal ischemia. The reported familial RTD with hypernephronic nephromegaly may be a specific disorder, but other forms could reflect renal ischemia acquired in utero or in early or later postnatal life.