Triosephosphate-Isomerase Deficiency: Epiphenomenon or Cause of Loin Pain Haematuria Syndrome?

A 32-year-old male patient presented the clinical picture of loin pain haematuria syndrome with pain attacks accompanied by macrohaematuria. In renal biopsy, the preglomerular vessels showed segmental wall hyalinosis in the sense of low-grade nephrosclerosis, and glomerular capillaries with slightly but diffusely thickened, non-split basal membranes on electron microscopy. Notable were irregularly deformed, different dense erythrocytes in the glomerular capillaries, and several tubular lumina.

Etiology of Kidney Diseases With Proteinuria in the Gambia/West Africa.

Unlabelled: In West Africa, kidney diseases are frequently seen, but diagnostic and therapeutic options are poor due to limited access to specialized facilities. To unravel the etiology and develop clinical guidelines, we collected clinical data and results of kidney biopsies in 121 pediatric and mostly young adult patients with edema and proteinuria in The Gambia. Workup included clinical examination, urine and serum analysis, and kidney biopsy findings.

Trends of renal diseases in Germany: review of a regional renal biopsy database from 1990 to 2013.

Background: Several renal biopsy registries in Europe have shown geographical and temporal variations in the patterns of renal diseases. However, there is a lack of current data on trends of renal disease in Central Europe.

Methods: After exclusion of transplant and re-biopsies, the renal biopsy registry of the German RWTH Aachen University Hospital included data of 1208 biopsies over a period of 24 years (1990-2013).

Erratum: Trends of renal diseases in Germany: review of a regional renal biopsy database from 1990 to 2013.

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Retrospective genetic analysis illustrates the spectrum of autosomal Alport syndrome in a case of living-related donor kidney transplantation.

Background: Kidney transplantation is the treatment of choice in end-stage renal disease due to Alport syndrome (AS). However, the chances of finding an adequate living-related donor in AS are much worse compared to non-heritable conditions. Successful cases of related living-donor transplantation mostly refer to X-linked AS but are rarely reported in genetically confirmed autosomal AS.

Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing.

A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy.

Thrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures.

An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy.

Thrombospondin type 1 domain-containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A receptor 1 (PLAR1). The prevalence of THSD7A-Ab-positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLAR1-Ab or THSD7A-Ab. We screened serum samples of 1276 patients with MN from three different cohorts for the presence of THSD7A-Ab by Western blot analysis and a newly developed indirect immunofluorescence test (IFT).

Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, and one-third of patients develop end-stage renal disease (ESRD). Circulating autoantibodies against the podocyte surface antigens phospholipase A2 receptor 1 (PLA2R1) and the recently identified thrombospondin type 1 domain-containing 7A (THSD7A) are assumed to cause the disease in the majority of patients. The pathogenicity of these antibodies, however, has not been directly proven.

Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome.

Nucleoporins are essential components of the nuclear pore complex (NPC). Only a few diseases have been attributed to NPC dysfunction. Steroid-resistant nephrotic syndrome (SRNS), a frequent cause of chronic kidney disease, is caused by dysfunction of glomerular podocytes.

Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy.

Background: Phospholipase A2 receptor antibodies (PLA2R-Ab) and thrombospondin type-1 domain-containing 7A antibodies (THSD7A-Ab) are present in 70-80% of patients with membranous nephropathy (MN). Little, however, is known about the pathogenesis of MN and the clinical outcome in PLA2R-Ab- and THSD7A-Ab-negative patients.

Methods: In this prospective multicentre observational study, the clinical outcome of 37 patients with biopsy-proven MN who were negative for PLA2R-Ab and THSD7A-Ab in the serum was analysed.

Response to cyclosporine in steroid-resistant nephrotic syndrome: discontinuation is possible.

Background: Steroid-resistant nephrotic syndrome (SRNS) is still regarded as a serious disease although treatment with cyclosporine (CSA) has improved outcome. However, the duration of treatment in responders is unclear, and treatment of patients with genetic causes is a matter of debate.

Methods: Thirty-six patients with SRNS were studied retrospectively.

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN.

ANCA-associated vasculitis is the most frequent cause of crescentic GN. To define new molecular and/or cellular biomarkers of this disease in the kidney, we performed microarray analyses of renal biopsy samples from patients with ANCA-associated crescentic GN. Expression profiles were correlated with clinical data in a prospective study of patients with renal ANCA disease.

Smaller caliber renal arteries are a novel feature of uromodulin-associated kidney disease.

Hyperuricemia is very common in industrialized countries and known to promote vascular smooth muscle cell proliferation. Juvenile hyperuricemia is a hallmark of uromodulin-associated kidney disease characterized by progressive interstitial renal fibrosis leading to end-stage renal disease within decades. Here we describe a member of a Polish-German family with a history of familial background of chronic kidney disease, hyperuricemia, and gout.

Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.

Background: Idiopathic membranous nephropathy is an autoimmune disease. In approximately 70% of patients, it is associated with autoantibodies against the phospholipase A2 receptor 1 (PLA2R1). Antigenic targets in the remaining patients are unknown.

CXCL5 drives neutrophil recruitment in TH17-mediated GN.

Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen- and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury.

Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.

The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy.

Renal IL-17 expression in human ANCA-associated glomerulonephritis.

Interleukin-17A (IL-17) promotes inflammatory renal tissue damage in mouse models of crescentic glomerulonephritis, including murine experimental autoimmune anti-myeloperoxidase glomerulonephritis, which most likely depends on IL-17-producing Th17 cells. In human anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, however, the cellular sources of IL-17 remain to be elucidated. Therefore, we analyzed human kidney biopsies of active necrotizing and crescentic ANCA-associated glomerulonephritis by immunohistochemistry using an IL-17-specific antibody and by immunofluorescent colocalization with cell type markers.

An immunofluorescence test for phospholipase-A₂-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis.

Background: The recent finding that phospholipase-A(2)-receptor antibodies (PLA(2)R-AB) may play a role in the development of primary membranous glomerulonephritis (MGN) offers the opportunity to measure a marker to help diagnose, classify and eventually monitor the course of patients with MGN.

Methods: We developed an immunofluorescence test, which allows the easy and specific analysis of the presence of PLA(2)R-AB in serum. The usefulness of this test was studied in 153 healthy blood donors, 90 patients with non-membranous glomerular injuries, 17 patients with a secondary form of MGN and 100 patients with biopsy-proven primary MGN.

Ubiquitin C-terminal hydrolase-l1 activity induces polyubiquitin accumulation in podocytes and increases proteinuria in rat membranous nephropathy.

Ubiquitin C-terminal hydrolase L1 (UCH-L1), a key protease of the ubiquitin-proteasome system (UPS), is associated with neurodegenerative diseases and cancer. Recently, de novo expression of UCH-L1 was described in podocytes in patients with membranous nephropathy (MN), in which UCH-L1 expression correlated with increased ubiquitin content. The objective of the present study was to investigate the role of UCH-L1 in ubiquitin homeostasis and proteasomal degradation in a rat model of MN.

Progressive renal insufficiency, hypercalcaemia, bicytopaenia and a history of breast cancer.

Sarcoidosis can affect all organs and may mimic a variety of other diseases. In the absence of typical pulmonary features, extrapulmonary manifestations may be difficult to diagnose. We describe here the very uncommon case of a patient with mild pulmonal involvement but distinct renal, bone marrow and lymph node sarcoidosis.

CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis.

Infiltration of T cells into the kidney is a typical feature of human and experimental lupus nephritis that contributes to renal tissue injury. The chemokine receptor CXCR3 is highly expressed on Th1 cells and is supposed to be crucial for their trafficking into inflamed tissues. In this study, we explored the functional role of CXCR3 using the MRL/MpJ-Fas(lpr) (MRL/lpr) mouse model of systemic lupus erythematosus that closely resembles the human disease.

Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases.

In renal tissue injury, activation of the transcription factor NF-kappaB has a central role in the induction of proinflammatory gene expression, which are involved in the development of progressive renal inflammatory disease. The function of NF-kappaB during the switch from the inflammatory process toward resolution, however, is largely unknown. Therefore, we assessed the time-dependent activation and function of NF-kappaB in two different models of acute nephritis.

Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice.

Angiotensin II (Ang II) activates at least two receptors, AT1 and AT2, with the majority of its effects-such as vasoconstriction, inflammation, and matrix deposition-mediated by the AT1 receptor. It is thought that the AT2 receptor counteracts these processes; however, recent studies have found proinflammatory and hypertrophic effects of this receptor subtype. To identify the physiological roles of the AT2 receptor in chronic kidney disease, we performed renal ablation in AT2 receptor knockout and wild-type mice.