Kidney Biopsy in Type 2 Diabetic Patients: Critical Reflections on Present Indications and Diagnostic Alternatives.

Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20-30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed "diabetic kidney disease" without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy.

Implanted blood vessel external support device (VasQ™) for creation of hemodialysis arteriovenous fistula: A single-center experience.

INTRODUCTION: the external support device VasQ is intended to promote arteriovenous fistula (AVF) maturation by maintaining the optimal anastomotic angle in order to minimize blood flow disturbances around the anastomotic area. The aim of the study is to assess efficacy and safety of the VasQ device both in brachiocephalic and radiocephalic fistulae. METHODS: a single institution prospective study was conducted with implantation of the VasQ device during AVF creation. Clinical and Doppler ultrasounds evaluations were performed at day-1, 1, 6, and 12 months for assessment of device-related adverse events, AVF maturation and patency. Moreover, volume flow rate and diameter of outflow vein were measured. A total of 16 patients were enrolled. Ten brachiocephalic and 6 radiocephalic AVFs were created with VasQ. Preoperatively cephalic vein diameter was 3.6 ± 0.9 mm. RESULTS: our population included 13 male and 3 females patients, 9 end stage kidney disease in conservative therapy, 4 dialysis treated patients, and 3 transplanted patients; mean age was 74.0 ± 8.1 years; no severe device-related adverse events were observed. Primary patency at 1, 6, and 12 months was 100%, 87.5%, and 67.7%, respectively, while secondary patency was 100%, 100%, and 78.3%, respectively. Comparing brachiocephalic to radiocephalic AVFs no significant differences in patency rates were seen. Overall maturation rate was 94% (15/16). Mean vein diameter measured with Doppler ultrasound at postoperative day-1 and at 1, 6, and 12 months was 5.0 ± 1.0, 5.9 ± 0.9, 7.2 ± 1.6, and 7.9 ± 1.4 mm, respectively, with a mean flow rate at the brachial artery of 841 ± 176, 1052 ± 224, 1261 ± 490, and 1348 ± 477 ml/min, respectively. CONCLUSIONS: in our limited experience VasQ was safe, with high maturation and patency rates. Positive results suggest a potential benefit for VasQ in AVF.

Novel avenues for treating diabetic nephropathy: new investigational drugs.

INTRODUCTION: At present, treatment of diabetic kidney disease (DKD) is still mainly based on drugs acting on glycemic and blood pressure control, as there is no validated therapy able to halt the progression of renal failure. Because of the high incidence of DKD, due to the increase of diabetes mellitus in general population, new therapeutic strategies are needed. Areas covered: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD. Expert opinion: Among the drugs currently being explored, the most promising molecules are those that interfere with glucose-dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs metabolic pathways, and impaired renal vascular regulation. One of the recent goals achieved by molecular biology is the development of monoclonal antibodies able to interfere with extracellular matrix accumulation and fibrosis. Other interesting therapies are under investigation and further studies with a greater number of patients will establish a better approach for diabetic nephropathy.

Renal biopsy: Still a landmark for the nephrologist.

Renal biopsy was performed for the first time more than one century ago, but its clinical use was routinely introduced in the 1950s. It is still an essential tool for diagnosis and choice of treatment of several primary or secondary kidney diseases. Moreover, it may help to know the expected time of end stage renal disease. The indications are represented by nephritic and/or nephrotic syndrome and rapidly progressive acute renal failure of unknown origin. Nowadays, it is performed mainly by nephrologists and radiologists using a 14-18 gauges needle with automated spring-loaded biopsy device, under real-time ultrasound guidance. Bleeding is the major primary complication that in rare cases may lead to retroperitoneal haemorrhage and need for surgical intervention and/or death. For this reason, careful evaluation of risks and benefits must be taken into account, and all procedures to minimize the risk of complications must be observed. After biopsy, an observation time of 12-24 h is necessary, whilst a prolonged observation may be needed rarely. In some cases it could be safer to use different techniques to reduce the risk of complications, such as laparoscopic or transjugular renal biopsy in patients with coagulopathy or alternative approaches in obese patients. Despite progress in medicine over the years with the introduction of more advanced molecular biology techniques, renal biopsy is still an irreplaceable tool for nephrologists.

Role of Vitamin D in Vascular Complications and Vascular Access Outcome in Patients with Chronic Kidney Disease.

Vitamin D has been known for a long time as a major factor involved in the calcium- phosphate balance and homeostasis, along with parathyroid hormone (PTH). While vitamin D effects on calcium and phosphate are fully known, recent studies attempted to link vitamin D status and cardiovascular diseases. The involvement of vitamin D on vascular remodeling is mediated by several mechanisms such as activation of renin-angiotensin-aldosterone system (RAAS), cell proliferation and anti-apoptotic cell pathways. This correlation is highlighted by the fact that the activated form of vitamin D (1,25 (OH)2 D3) can be synthesized by the same endothelial cells, due to the constitutive presence of endothelial 1α-hydroxylase. Vitamin D reduces the expression of angiotensin 2 receptor (AT2R) on the endothelial cell surface (AT2R), leading to a cascade of events that result in the synthesis of vasodilators, such as nitric oxide. The activation of vitamin D receptors (VDRs) on endothelial cells induces changes in the metabolic activity of the endothelium and is responsible for cell survival, proliferation and neoangiogenesis. Moreover, altered signaling of VDR due to gene polymorphisms has been demonstrated in patients with cardiac disorders and chronic kidney disease (CKD). Recently, vascular access outcome has been associated with vitamin D status. Future studies will help to better define the need of vitamin D supplementation for a better cardiovascular as well as vascular access outcome in patients with CKD.

An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease.

INTRODUCTION: At present, treatment of autosomal dominant polycystic kidney disease (ADPKD) is essentially supportive as there is still no specific therapy. However, recent advances with ADPKD pathophysiology have stimulated research for new therapeutic strategies. AREAS COVERED: The aim of this systematic review is to analyze the experimental and early investigational therapies currently under evaluation in this field. Data from completed clinical trials were retrieved from the currently available scientific literature and from the ClinicalTrials.gov website. EXPERT OPINION: Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

Monoclonal antibodies for renal diseases: current concepts and ongoing treatments.

INTRODUCTION: In recent years, technological innovations in the field of molecular biology have provided new therapeutic options. In particular, human monoclonal antibodies (mAbs), initially used in the treatment of malignancies, have become a therapeutic tool for many other diseases. Most of the application of mAbs revealed encouraging findings to treat patients with immune-mediated glomerular diseases, for whom the standard protocols based on corticosteroids and non-specific immunosuppressants with heavy side effects have for decades been the only therapies. AREA COVERED: Rituximab, an mAb directed against a specific antigen expressed on B lymphocytes, CD20 antigen, inducing a premature cell apoptosis became very important in the treatment of membranous glomerulonephritis, steroid-resistant nephrotic syndromes and membranoproliferative glomerulonephritis (MPGN). Another important mAb, eculizumab, is used successfully for treatment of atypical hemolytic uremic syndrome, C3 nephropathy and MPGN. Many other mAbs are now under premarketing investigation, such as adalimumab, daclizumab, fresolimumab, belimumab, tocilizumab, although some of these mAbs are already approved for different medical applications. EXPERT OPINION: The availability of novel mAb may therefore constitute the basis for a revolution in the treatment of immune-mediated renal diseases. However, the cost for this therapy remains very high and represents a barrier for its widespread use.