Search

The development of well-tolerated and effective therapies that target the pathogenesis of membranous nephropathy (MN) would be useful. Our objective was to evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients treated with rituximab for idiopathic MN. Anti-PLA2R antibodies in serum and PLA2R antigen in kidney biopsy were assessed in 10 and 9 patients, respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6 and 12 months, respectively. At 6 months, 2 patients achieved complete remission (CR) and 12 partial remission (PR; overall renal response, 50%). At 12 months (n = 23), CR was achieved in 6 patients and PR in 13 patients (overall renal response, 82.6%). Three patients suffered a relapse of nephrotic proteinuria 27–50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD estimated glomerular filtration rate 2) is an independent factor that predicts lack of response to rituximab. Anti-PLA2R antibodies were detected in the serum of 10 patients, and PLA2R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up sera. In this retrospective study, a high rate of remission was achieved 12 months after treatment.

Gene therapy is obviously a controversial issue and a wave of suspicion has dampened the initial enthusiasm raised by this new therapeutic approach. It has now become fashionable to downplay the potential for gene therapy in most fields including kidney-related diseases. In our opinion, this is an unfair and unrealistic view of the future. In fact, gene therapy of well-selected kidney diseases will certainly become feasible, but a large data base on vectors and transfer methods both in the normal kidney and in disease models has first to be collected. Any significant progress in the biology of the vectors, in the cellular interactions of the newly introduced DNA, and in the regulation and persistency of the transgene should be rapidly translated to the kidney in relevant experimental models. Herein, we present the use and current limitations of gene transfer to the kidney and the potential therapeutic perspectives.

Glomerular injury can be caused by numerous insults including hemodynamics, infections and immunity, hereditary and metabolic diseases, and toxicity. Basic and translational experimental studies in combination with clinical research in patients with renal disease have advanced our understanding of the etiology and pathogenesis of many forms of glomerulonephritis. This new knowledge has facilitated classification and treatment and has contributed to a better outcome of patients with renal disease. Since renal disease almost without exception leads to systemic cardiovascular complications, these advances are also of general health interest. Here, we shall briefly review general principles in the pathology of glomerular injury and discuss recent developments in the study of podocytopathies; membranous glomerulopathy; ANCA-associated vasculitis; C3 glomerulopathies and the role of complement in endothelial injury; and the prognostic value of the renal biopsy in predicting long-term outcome in lupus nephritis, vasculitis and IgA nephropathy.

Light, light and heavy, and heavy chain deposition diseases (LCDD, LHCDD and HCDD, respectively) belong to a family of diseases featuring deposition in the kidney of a monoclonal immunoglobulin (Ig) or its isolated subunits, which also includes light chain amyloidosis, non-amyloid fibrillary and immunotactoid glomerulonephritis, and cryoglobulinemic glomerulonephritis. In clinical and pathologic terms, LCDD, LHCDD and HCDD display essentially similar characteristics, such as involvement of multiple organs, prominent renal involvement with severe renal failure, diabetes-like nodular glomerulosclerosis, marked thickening of tubular basement membranes, and monotypic deposits of Ig light chains (mostly κ) and/or heavy chains (mostly γ) that feature a non-organized granular, electron-dense appearance by electron microscopy. The most common cause is myeloma, although in a fair proportion of cases there is no (clinically) patent hematological disease. Recent progress has been made in understanding the molecular mechanisms of Ig-chain deposition and extracellular matrix accumulation, which opens up new therapeutic avenues in addition to eradication of the Ig-secreting plasma cell clone. Because these diseases represent a model of glomerular and interstitial fibrosis that is induced by a single molecule species, a better understanding of their pathophysiological mechanism may help unraveling the pathomechanisms of kidney fibrosis and renal disease progression.

Ureteral stenosis is unusual in Wegener’s granulomatosis. We describe a case in which surgical intervention enabled the diagnosis to be made and appropriate treatment to be given.

A patient with ocular hypertension was treated with acetazolamide. Acute renal failure developed rapidly and renal biopsy showed mild tubular lesions and crystal formation in a tubular lumen. By immunofluorescence studies with a monoclonal antibody, Tamm-Horsfall protein, normally absent from the proximal segments of the nephron, was detected in most glomeruli. This strongly suggests that tubular obstruction plays a major part in some cases of acetazolamide-induced acute renal failure.