Glomerular Capillary Lumen Research Articles

Intracapillary monoclonal IgM deposits disease with massive pseudothrombi: A clinicopathologic study of 4 cases and literature review.

Intracapillary monoclonal IgM deposits disease (ICMDD) has long been considered a hallmark of Waldenström macroglobulinemia (WM) nephropathy. Intracapillary immunoglobulin thrombi are the characteristic features of cryoglobulinemic glomerulonephritis. Here, we reported 4 cases of ICMDD with massive pseudothrombi but without WM or cryoglobulinemia. We retrospectively analyzed the clinical and pathologic features of patients diagnosed with ICMDD with massive pseudothrombi. A total of 4 patients (2 men and 2 women) aged 62 to 73 years were enrolled in this study. Microscopic hematuria, edema, and renal insufficiency were present in all patients, along with low serum C3 and C4 in 2 patients. Hematologic examination showed abnormal serum free light chain ratios in all patients and high levels of serum IgM in 3 patients. IgM-κ monoclonal band was identified by serum immunofixation electrophoresis in 3 patients. One patient was diagnosed with small B-cell lymphoma by bone marrow aspiration. Renal biopsy specimen showed massive periodic acid-Schiff-positive hyaline thrombi in the glomerular capillary lumens and also less mesangial, subendothelial, and subepithelial deposits on light microscopy. Immunofluorescence indicated positive staining for IgM (++) and κ light chain staining in the glomerular capillary lumens, capillary walls, and mesangium in all patients. By electron microscopy, the glomerular capillary lumens were filled with homogeneous high-electron-dense deposits without substructure. Two patients were treated with prednisone combined with cyclophosphamide, and 2 received plasma cell-targeted chemotherapy. One patient achieved partial renal remission. Intracapillary monoclonal IgM deposits disease is a rare disease and not always related to WM. Most patients have IgM monoclonal immunoglobulinemia; renal biopsy specimens mainly show a large number of pseudothrombi in the glomerular capillary lumens. Cyclophosphamide is effective in some patients.

Lipoprotein glomerulopathy: what is known? Literature review

The review is devoted to the important problem of contemporary nephrology — lipoprotein glomerulopathy (LPG), a rare glomerular disorder leading to nephrotic syndrome and/or chronic kidney failure (CKF). The article highlights the primary genetic defect in LPG associated with heterozygous mutations of the apolipoprotein E (ApoE) gene in the low‑density lipoprotein (LDL) binding site with the corresponding receptor, which increases the affinity of mutant ApoE‑containing lipoproteins to the glomerular capillary wall. The article presents data from population‑based studies on the prevalence of LPG and current understanding of its pathogenesis, in particular, the main pathogenetic link — damage to the structure and function of ApoE due to heterozygous mutations of the ApoE gene. The participation of ApoE‑containing lipoproteins, which include ApoE isoforms, in the formation of glomerular deposits, lipoprotein thrombi in the lumen of glomerular capillaries, as well as the role of macrophages in the pathogenesis of renal lipidosis is considered. Histological picture typical for LPG, intraglomerular and extrarenal factors of its development, and features of serum lipid spectrum accompanying the clinical course of LPG are described. Diagnostic criteria of LPG, clinical manifestations of this glomerular disorder, prognosis in LPG, its complications and some co-morbid states associated with LPG are given. Special attention is paid for the treatment of LPG, without which the disease is progressing to a terminal CKF. Some possibilities of contemporary lipid lowering agents (fibrates, nicotinic acid derivates, statins, monoclonal antibodies to apolipoprotein CIII) in correction of lipid disorders associated with LPG are discussed. Some perspective agents that could be applied in patients with LPG (inhibitors of natrium-dependent glucose co-transporter 2, antioxidants, anticonvulsant topiramate) after special trials are enumerated. Some attention is paid to other treatment measures in LPG, such as LDL-apheresis with heparin‑induced extracorporal precipitation, staphylococcal protein-A immunoadsorption therapy, and renal transplantation. Necessity is emphasized of further experimental and clinical studies that will allow to enlarge updated ideas about the etiology and pathogenesis of LPG, improve its diagnostics and treatment efficacy.

Clinicopathological characteristics and gene mutations in 11 patients with lipoprotein glomerulopathy

Objective Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. Methods Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. Results The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. Conclusion LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Correlation of light and electron microscopic morphometric parameters of glomerular capillaries with serum creatinine and proteinuria

ABSTRACT Waste products in the bloodstream are filtered by the glomerular capillaries in the kidneys and excreted into the urine. When making a differential diagnosis of kidney diseases, structural assessment of glomeruli using histological, ultrastructural, and immunological studies is crucial. This study assessed the microscopic and ultrastructural morphometric parameters of glomerular capillaries and examined their correlation with serum creatinine and proteinuria. A total of 60 kidney biopsy cases received by the transmission electron microscope (TEM) laboratory for diagnosis were included in the study. Toluidine blue stained 300 nm thick sections of TEM tissue blocks were scanned for glomerular morphometry by a whole slide imaging system, and the estimation of Bowman’s capsule (BC) area, glomerular capillary lumen diameter (GCLD), glomerular capillary density (GCD), glomerular capillary surface area density (GCSA), and percentage of glomerular capillary lumen space (%GCLS) was performed with QuPath software. TEM images of 70 nm thick sections were used for the evaluation of endothelial fenestration diameter (EFD), glomerular basement membrane (GBM) thickness, and podocyte foot process (PFP) effacement. Proteinuria and serum creatinine showed positive correlations with GBM thickness and PFP effacement. Negative correlations of serum creatinine were observed with EFD, %GCLS, and GCSA. Hence, glomerular filtration is greatly affected by the total area of the glomerular capillary surface and structural changes of GBM. Reduction of glomerulus filtration due to foot process effacement and thickening of GBM results in damage to the filtration barrier leading to the leakage of plasma protein into urine.

A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib

BackgroundGlomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton’s tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy.Case presentationThe patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy.ConclusionsCLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

Carfilzomib Is Safe in Elderly Patients with Multiple Myeloma but Thrombotic Microangiopathy Is Underestimated in Clinical Practice

IntroductionCarfilzomib (K or Cfz) is a widely used second-generation proteasome inhibitor for patients with multiple myeloma (MM). However, despite the numerous positive clinical results, there were only a few “real-world” studies, particularly among elderly patients. Avoiding Cfz for the elderly may be based on a potential selection bias to avoid rare but serious cardiovascular adverse events (CVAEs) associated with Cfz. Moreover, although Cfz-associated thrombotic microangiopathy (TMA) has been recently recognized, the incidence rate of TMA varied from less than 1% to 5.0%. To determine the efficacy of Cfz and occurrence of CVAEs in the elderly patients and the incidence of TMA, we reviewed 96 patients, including 28 elderly patients (aged ≥76 years) at our center. All participants or their family members provided written informed consent for inclusion in the study. The study was conducted according to the Declaration of Helsinki and approved by the ethical review board of our institute.MethodsCfz was administered in the same protocol as in each clinical trial. The choice of the Cfz regimen and the criteria for dose reduction, including dexamethasone use, were based on the patient's background and discretion of the treating physician.Severe CVAEs were defined as events of grade ≥3 including heart failure, acute coronary syndrome, relative reduction in the left ventricular ejection fraction ≥20% from baseline, QT prolongation (corrected QT: ≥501 ms), and hypertension (systolic blood pressure of ≥160 mm Hg and/or diastolic blood pressure of ≥100 mm Hg, requiring two or more additional intensive medications than before) that were observed within three months after the initiation of Cfz therapy. The diagnosis of TMA was made as follows: when clinical findings were consistent with microangiopathic hemolytic anemia, such as thrombocytopenia, progressive anemia with schistocytes, elevated lactate dehydrogenase, and other differential diseases, including bacteremia or tumor progression, could be excluded.ResultsThe patients' median age at Cfz initiation was 71 (range, 30-91) years. In total, 96 (100%), 86 (89.6%), 22 (22.9%), and 23 (23.9%) patients received bortezomib, lenalidomide, daratumumab, and autologous stem cell transplantation before Cfz therapy.Until the end of the study, 13 CVAEs (13.5%) of grade ≥3 were observed, including 2 (11.1%), 1 (11.1%), and 10 (15.2%) in patients who received Kd (Cfz and dexamethasone), DKd (Daratumumab, Cfz, and dexamethasone), and KRd (Cfz, lenalidomide, and dexamethasone), respectively. Despite the use of appropriate supportive care, grade ≥3 AEs resulting in Cfz withdrawal were noted in 25 patients: CVAEs in 11, thrombocytopenia in 4, TMA in 3, and infection in two patients. Notably, one patient with end-stage myeloma who received KRd 20/27 mg/m 2 died of CVAE on day 10 of cycle 1.At Cfz initiation, 28 patients were aged 76-80 (n=14) and ≥81 years (n=14) (Fig. 1). Three elderly patients had severe CVAEs (10.7%). The median numbers of prior chemotherapy to Cfz, time to next treatment, and overall survival from Cfz initiation were 2.5, 28.0, and 41.1 months, respectively. Although 10 patients (35.7%) discontinued Cfz therapy due to disease progression, only four patients (14.3%) discontinued Cfz owing to grade ≥3 AEs, including TMA (n = 1) and CVAEs (n = 3).Overall, five patients (5.2%) showed TMA. All patients received Kd-based regimens upon TMA development (Kd, n = 2 and DKd, n = 3). The median age of the patients who developed TMA was 74 years, and the Cfz dose was 20/27 in 1, 20/36 in 1, and 20/56 mg/m 2 in three patients. Although three patients developed TMA during the first Cfz cycle (on days 11, 16, and 21, respectively), two patients received KRd therapy before the Kd therapy that caused TMA. Two patients required temporary dialysis and four patients discontinued Cfz therapy. Eculizumab was administered in a patient and a kidney biopsy showed that the lumen of most glomerular capillaries was occluded by fibrin thrombi (Fig. 1). Furthermore, the vessel in the vascular pole of the glomerulus had necrotic lesions, suggesting drug-induced and complement-mediated TMA.ConclusionCfz could be used safely in the elderly patients. The incidence of CVAEs by Cfz in elderly patients was similar to that in the entire cohort. The incidence of TMA was 5.2%, and Cfz-induced TMA should be carefully considered, particularly in patients using high-dose Cfz. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The adverse effect of long term intake of Monosodium Glutamate on kidney performance

Monosodium glutamate (MSG) is a food additive that is considered as a water and environmental pollutant and affects the tissues of the living being. This study was aimed to find the effect of long-term administration of MSG on the mass of mesangial cells of the kidneys. Forty adult male rats were divided into four groups (10 each). Control groups 1&2 were supplied orally with distilled water for 30 and 60 days, respectively. Treatment groups 1&2 were supplied orally with 15 mg/kg Bwt of MSG for 30 & 60 days, respectively. Control and treatment groups were sacrificed, specimens of kidneys were obtained, fixed with 10% neutral buffered formalin, processed by Routine histological techniques, stained by Hematoxylin and eosin, and PAS (Periodic Acid-Schiff) stains then examined under the light microscope. The result found enlargement in a mesangial mass represented by hypertrophy and hyperplasia of mesangial cells leading to mesangial proliferative glomerulonephritis. Accordingly, the study showed an increase in creatinine values, indicating a disturbance in renal function. This will lead to a decrease in the sizes of the glomeruli of renal corpuscles and a relative increase of Bowman’s space. With the time of the experiment, the glomerular capillaries and gates of basement membranes will be closed, resulting in renal filtration disorders. It was concluded that the long-term intake of MSG leads to indirect narrowing of the glomerular capillary lumen, causing kidney failure.

Nephrotoxicity of Antimicrobials and Antibiotics.

Medication-induced nephrotoxicity remains one of the most common causes of acute kidney injury (AKI) among hospitalized patients. Within the extensive group of medications associated with AKI, antibiotics and other antimicrobials are well recognized triggers of structural and functional renal impairment. Clinical manifestations range from mild forms of tubular injury to significant deterioration of kidney function requiring acute renal replacement therapy. Several mechanisms are described, although the most frequent are acute interstitial nephritis, acute tubular necrosis, intratubular crystal deposition, and proximal/distal tubulopathy with electrolyte wasting abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease, and concomitant use of medication with nephrotoxic potential. Prevention and early recognition of AKI represent the standard approach to mitigate AKI and avoid morbidity.

Infusing Mesenchymal Stromal Cells into Porcine Kidneys during Normothermic Machine Perfusion: Intact MSCs Can Be Traced and Localised to Glomeruli.

Normothermic machine perfusion (NMP) of kidneys offers the opportunity to perform active interventions, such as the addition of mesenchymal stromal cells (MSCs), to an isolated organ prior to transplantation. The purpose of this study was to determine whether administering MSCs to kidneys during NMP is feasible, what the effect of NMP is on MSCs and whether intact MSCs are retained in the kidney and to which structures they home. Viable porcine kidneys were obtained from a slaughterhouse. Kidneys were machine perfused during 7 h at 37 °C. After 1 h of perfusion either 0, 105, 106 or 107 human adipose tissue derived MSCs were added. Additional ex vivo perfusions were conducted with fluorescent pre-labelled bone-marrow derived MSCs to assess localisation and survival of MSCs during NMP. After NMP, intact MSCs were detected by immunohistochemistry in the lumen of glomerular capillaries, but only in the 107 MSC group. The experiments with fluorescent pre-labelled MSCs showed that only a minority of glomeruli were positive for infused MSCs and most of these glomeruli contained multiple MSCs. Flow cytometry showed that the number of infused MSCs in the perfusion circuit steeply declined during NMP to approximately 10%. In conclusion, the number of circulating MSCs in the perfusate decreases rapidly in time and after NMP only a small portion of the MSCs are intact and these appear to be clustered in a minority of glomeruli.

Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation

The coordination of multiple cytokines and transcription factors with their downstream signaling pathways have been shown to be integral to nephron maturation. Here we present a completely novel role for the helix-loop-helix transcription factor Early B cell Factor 1 (Ebf1), originally identified for B cell maturation, for the proper maturation of glomerular cells from mesenchymal progenitors. The expression of Ebf1 was both spatially and temporally regulated within the developing cortex and glomeruli. Using Ebf1-null mice we then identified biochemical, metabolic, and histological abnormalities in renal development that arose in the absence of this transcription factor. In the Ebf1 knockout mice the developed kidneys show thinned cortices and reduced glomerular maturation. The glomeruli showed abnormal vascularization and severely effaced podocytes. The mice exhibited early albuminuria and elevated blood urea nitrogen levels. Moreover, the GFR was reduced over 66 percent and the expression of podocyte-derived VEGF-A was decreased compared to wild type control mice. Thus, Ebf1 has a significant and novel role in glomerular development, podocyte maturation, and the maintenance of kidney integrity and function.

In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells

Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co-cultured with oxidant-injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co-cultured with injured mesangial cells had a mesangial cell-like morphology and contracted in response to angiotensin II. They expressed CD54(-) CD62E(+) in direct contrast to the CD54(+) CD62E(-) of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co-cultured with injured mesangial cells.

Cytomegalovirus Glomerulopathy and Cytomegalovirus Interstitial Nephritis on Sequential Transplant Kidney Biopsies

Cytomegalovirus (CMV) nephropathy may be seen in kidney transplant biopsy specimens. We report a CMV-negative patient who received a kidney transplant from a CMV-positive donor and subsequently developed CMV glomerulopathy and CMV-associated interstitial nephritis, as observed in 2 sequential kidney biopsies. The first biopsy specimen showed CMV-positive endothelial cells in glomerular capillaries and CMV-infected monocytes in glomerular capillary lumens. The second biopsy specimen showed CMV-positive cells in the interstitium with associated lymphoplasmacytic infiltrate and tubular injury, but no evidence of direct CMV infection in tubular epithelial cells. Moreover, the second biopsy specimen showed persistent monocytes with cytoplasmic viral particles within glomerular capillary loops by electron microscopy. Our case shows that CMV glomerulopathy can be caused by direct CMV infection of glomerular capillary endothelial cells. CMV-positive circulating monocytes may play an important role in the different histopathologic manifestations of CMV nephropathy in kidney transplant grafts.

Proliferative glomerulonephritis with monoclonal IgM deposits without Waldenström’s macroglobulinemia: case report and review of the literature

A 38-year-old man was presented with nephrotic syndrome associated with hematuria and mild hypocomplementemia. Renal biopsy revealed lobular mesangial proliferation, thickened capillary walls, and intraluminal protein thrombi. Immunofluorescence showed marked and mild depositions of immunoglobulin (Ig) M heavy chains and complement C3, respectively, in a peripheral lobular pattern. On light chain staining, only kappa (κ) light and IgM heavy chains showed a similar pattern. Electron microscopy showed fine granular electrondense deposits in subendothelial areas and numerous globular deposits (varying size and density) in glomerular capillary lumens. Serum levels of Ig κ, but not of free κ, light chains were significantly increased. Bone marrow aspiration revealed a normocellular marrow. Waldenström's macroglobulinemia and cryoglobulinemia were ruled out. Clinically, steroid therapy was ineffective and proteinuria persisted. This report demonstrates that glomerular deposition of monoclonal IgM-κ can produce membranoproliferative- like changes in the glomeruli. This condition may be recognized as proliferative glomerulonephritis with monoclonal IgM deposits similar to the recently recognized proliferative glomerulonephritis with monoclonal IgG deposits.

A Novel Apolipoprotein E Mutation, ApoE Osaka (Arg158 Pro), in a Dyslipidemic Patient with Lipoprotein Glomerulopathy

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by the presence of thrombuslike deposition in markedly dilated glomerular capillaries and is often accompanied by an increased serum apolipoprotein E (apoE) level. Several gene mutations of apoE have been reported to be associated with LPG. In the current study, we report an LPG patient with a novel apoE mutation, apoE Osaka. The patient was a 45-year-old man who was hospitalized due to nephrotic syndrome. Light and electron microscopic observations of renal biopsy clearly showed characteristic findings of LPG, including lamellate thrombi in the lumen of dilated glomerular capillaries. His apoE phenotype was apoE3/2 and he had mild dyslipidemia with a mid-band on polyacrylamide gel electrophoresis. It is intriguing that the serum apoE level was within normal limits. We determined the sequence of the apoE gene using direct sequencing of the polymerase chain reaction (PCR) products. ApoE gene analysis showed a nucleotide substitution of G to C at codon 158 of exon 4. This mutation denoted an amino acid substitution of arginine residue for the proline residue at position 158 of apoE. The result of PCR associated with restriction fragment length polymorphism analysis also suggested that this mutation is heterozygous. It is possible that apoE Osaka mutation causes a conformational change of apoE protein and affects the interaction between abnormal apoE-containing lipoproteins and the endothelial cells of glomerular capillaries. The precise mechanism of LPG related with apoE Osaka, however, remains to be elucidated.

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

Lipoprotein glomerulopathy (LPG) is a rare hereditary disease characterized by the accumulation of much thrombi material consisting of lipoproteins at the glomerular capillary lumen. Most patients show nephrotic syndrome; nearly half progress to chronic renal failure. Intensive therapy with lipid-lowering agents reportedly engenders clinical remission with histological resolution. We report the case of a 14-year-old Japanese female patient who had been in a nephrotic condition with hematuria from 4 years old and who had been diagnosed based on pathological and molecular examination at 7 years old. We initially treated the patient with probucol, enalapril (angiotensin-converting enzyme inhibitor: ACEI), and dipyridamole from age 7, but achieved no improvement in her nephrotic status. Subsequently, we replaced probucol with bezafibrate at age 11 and added atorvastatin calcium hydrate and valsartan (angiotensin II receptor blocker: ARB) the following year. The next 3 years' treatment improved her nephrotic status, decreased serum apolipoprotein E, and markedly decreased intraglomerular lipoprotein thrombi. Early and intensive therapy with antilipidemic drugs combined with ACEI and ARB is inferred to be effective for LPG.

Immunoglobulin A nephropathy associated with juvenile dermatomyositis

Sirs, We read with great interest the article in Pediatric Nephrology entitled “Pathophysiological lessons from rare associations of immunological disorders” by Ronco and Debiec [1], following the admission of a patient with juvenile dermatomyositis (JDM) and immunoglobulin A (IgA) nephropathy to our department. A 14-year-old girl presented with a 2-month history of skin rash, fever, muscle weakness and generalized myalgia. Physical examination revealed a heliotropic rash (purplepink in colour) over the eyelids and Gottron’s papules over the extensor surfaces of the wrist and over the dorsal interphalangeal and metacarpophalangeal joints (Fig. 1a). She also had severe weakness and tenderness of the muscles, including the bilateral deltoid muscles, femoral muscles and pelvic girdle. Her erythrocyte sedimentation rate (42 mm/h) and Creactive protein level (8 mg/dl) were increased. Elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) were found: 233 U/l (normal, <40 U/l), 317 U/l (normal, <40 U/l), 679 U/l (normal, 125– 243 U/l) and 529 U/l (normal, 34–174 U/l), respectively. Serum urea, creatinine, albumin, anti-streptolysin O titre, complement levels (C3 and C4) and serum immunoglobulins (IgG, IgA, IgM and IgE) levels were within normal limits. Findings for auto-antibodies, including rheumatoid factor (RF), anti-nuclear antibody (ANA), anti-doublestranded (anti-ds) DNA, perinuclear anti-neutrophilic cytoplasmic antibody (p-ANCA), cytoplasmic anti-neutrophilic cytoplasmic antibody (c-ANCA) and anti-extractable nuclear antigen (anti-ENA) (anti-Ro, anti-La, anti-Sm, anti-RNP, anti-Scl-70 and anti-Jo-1) were all negative. Urinalysis revealed protein (3+) and blood (1+), and the sediment contained 25–30 red cells per high-power field. Urinary protein excretion was 743 mg/day (580 mg/m per day). Electromyography (EMG) of bilateral deltoid, biceps femoris, iliopsoas and quadriceps muscles demonstrated polyphasic patterns with decreased amplitude and duration, indicating acquired myopathic inflammation. Magnetic resonance spectroscopy (MRS) of the thigh showed decreased creatine peak and elevated choline and myoinositol peaks, reflecting muscle inflammation (Fig. 1b). Based on clinical findings and laboratory examinations, a diagnosis of juvenile dermatomyositis was made. Oral treatment with prednisolone (2 mg/kg per day) and methotrexate (15 mg/m per week) was started. A percutaneous renal biopsy was performed on the 15th day of admission due to persistence of the proteinuria. Twenty-five glomeruli were obtained and showed proliferation of mesangial cells and an increased area of mesangial matrix (Fig. 1c). The glomerular capillary lumens were patent, with normal tubuli and arterioles. There was no cresent and/or fibrosis. Immunofluorescence microscopy revealed segmental deposits of IgA (3+) in the mesangium (Fig. 1d) and was negative for IgG, IgM, C3, C1q and Pediatr Nephrol (2009) 24:2073–2075 DOI 10.1007/s00467-009-1178-x

Renal intravascular large B-cell lymphoma with early diagnosis by renal biopsy: A case report and review of the literature

Intravascular large B-cell lymphoma (IVLBCL) is a rare entity of lymphoma. We report a case of IVLBCL presenting as renal dysfunction which was diagnosed by renal biopsy. Histopathological examination of the renal biopsy specimens showed dissemination of lymphoma cells throughout the glomerular capillary lumens. The cells were CD5−, CD10−, CD20+, BCL2+, BCL6+, and MUM-1+. Rituximab-chemotherapy was performed and complete response was achieved. With the accumulation of cases, establishment of a treatment strategy for IVLBCL is expected in the future. We could perform early diagnosis by renal biopsy and were able to achieve long-term remission by rituximab combination chemotherapy.

Evaluation of histologic changes in the urinary tract of hypercalciuric rats

Idiopathic hypercalciuria (IH) has been speculated to have a predisposing role in the development of urinary tract infection (UTI), due to the uroepithelial cell damage it leads to. In this study, we aimed to investigate the effects of hypercalciuria on the bladder, ureters, and kidneys in rats with experimentally induced hypercalciuria.Normocalcemic hypercalciuria was induced by furosemide (60 mg/100 mL of drinking water) administration to 16-week-old male Wistar Albino rats for 14 days. Calciuria (calcium/creatinine ratio, mg/mg, Ca/Cr) increased from 0.07+/-0.01 at the beginning of administration to 0.41+/-0.1 on day 14 (p=0.000). The Ca/Cr ratio was 0.14+/-0.06 at the beginning of the study and 0.25+/-0.06 on day 14 in the control group rats (p=0.002 vs. the hypercalciuric group rats on day 14). Bladder, ureter, and kidney specimens of the rats, dissected on the 14th day, were fixed in 10% formalin and 2.5% gluteraldehyde solutions for light and electron microscopic examination, respectively. Histopathological and ultrastructural examination of the hypercalciuric rats revealed proliferation and apical cytoplasmic vacuole formation in transitional epithelial cells, mitotic activity in the intermediate cell line, vasodilatation, edema, and separation of collagen fibers in the bladder and ureter specimens. Light microscopic examination of the kidney specimens revealed a lot of erythrocyte in the glomerular capillary lumen, while electron microscopy revealed vacuolization of proximal and distal tubules, tubular degeneration, interstitial edema, and vasodilatation.In this study, hypercalciuria was observed to have adverse effects on the cell architecture of the uroepithelium and disruption of the epithelial barrier of the bladder and ureters and all kidney structures, especially on the proximal epithelial cells.

Acute Renal Failure due to IgM-λ Glomerular Thrombi and MPGN-Like Lesions in a Patient With Angioimmunoblastic T-Cell Lymphoma

A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM-lambda). Renal biopsy showed membranoproliferative glomerulonephritis-like lesions with azan-red-stained thrombi in the glomerular capillary lumen. Immunofluorescence showed that IgM-lambda stained strongly in the glomerular capillary lumen, equal to the azan-red-stained thrombi, whereas C3 and C4 staining was negative. Electron microscopy showed electron-dense deposits in the subendothelial space and glomerular thrombi lacking fine fibrillar structure. These findings suggest that cryoglobulin, which consists of monoclonal IgM-lambda, induced glomerular thrombi and acute renal failure in a patient with angioimmunoblastic T-cell lymphoma.

Para-capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases

Electron-dense deposits are often found around glomerular capillary lumens in patients with glomerulonephritis, forming a portion of the blood-urine barrier (BUB). Four hundred and four patients with primary glomerular diseases or donors for living-related kidney transplantation who underwent both percutaneous renal biopsy and renal clearance tests were included in the study. Sodium thiosulfate and paraamino hippurate double-clearance studies were performed with catheterized urinary collection. The filtration fraction (FF) was determined as follows: FF = sodium thiosulfate clearance/paraamino hippurate clearance (CPAH: ). Histomorphometric analyses were performed in 53 patients with overt para-capillary electron-dense deposits (PCEDD) by electron microscopic observations. Patients with membranous nephropathy and membranoproliferative glomerulonephritis showed significantly lower levels of FF than the donors for living-rebated kidney transplantation (normal controls). FF levels were significantly lower in patients with PCEDD than in those without (P < 0.001), while the levels of mean blood pressure and CPAH: were comparable in the two groups. The PCEDD/BUB ratio demonstrated a significant negative correlation with FF (P < 0.0001; r(2) = 0.331). Patients with a ratio of 0.5 or more showed significantly lower FF levels than those with a ratio of 0.25 or less. PCEDD significantly affected FF levels in patients with primary glomerular diseases. FF may not be an accurate indicator of intraglomerular blood pressure in patients with overt PCEDD.