Diagnostic Pitfalls of the Bleeding Origin after a Percutaneous Renal Biopsy: A Report of Two Cases.

A percutaneous renal biopsy (PRB) is a standard procedure for diagnosing renal disease, but can cause bleeding complications. Bleeding after a PRB can be classified as early- or late-onset, depending on the timing of the onset of the bleeding symptoms (<24 h or ≥24 h). We herein report two patients who experienced bleeding complications: one experienced early-onset bleeding from the 12th subcostal artery, and the other experienced late-onset bleeding from an arteriovenous fistula between a branch of the renal artery and renal vein. In both cases, the origin of the bleeding vessel was misjudged during the first examination. We discuss the diagnostic pitfalls of the origin of bleeding after a PRB and propose measures to avoid falling such pitfalls.

Anti-contactin 1 Antibody-associated Membranous Nephropathy in Chronic Inflammatory Demyelinating Polyneuropathy with Several Autoantibodies.

A 50-year-old man diagnosed with anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was referred to our department for the evaluation of proteinuria. A kidney biopsy revealed membranous nephropathy (MN). Immunohistochemistry for CNTN1 revealed positive granular staining along the glomerular basement membrane, confirming anti-CNTN1 antibody-associated MN. Immunofluorescence showed a full-house pattern, and several autoantibodies, such as anti-nuclear antibody, anti-double-strand DNA antibody, and anti-cardiolipin antibody, were detected in the patient's serum. Although limited autoantibodies have been investigated in some of the reported cases, a variety of autoantibodies might be produced in anti-CNTN1 antibody-associated CIDP, accompanied by MN.

A Rare Case of Sporadic Medullary Cystic Kidney Disease with Rapidly Progressive Renal Dysfunction and Renal Enlargement Complicated by Idiopathic Nodular Glomerulosclerosis.

An 81-year-old man with hypertension and a history of smoking presented with renal enlargement and progressive renal dysfunction despite no family history of kidney disease. A renal biopsy revealed diffuse tubular, dilated, and atrophic distal tubules with cystic formation and thin irregularities in the tubular basement membrane. Although no known genetic abnormalities were detected, the patient was diagnosed with medullary cystic kidney disease (MCKD). In addition, idiopathic nodular glomerulosclerosis, which is characterized by significant mesangial expansion and accentuated glomerular nodularity and is associated with hypertension and cigarette smoking, was identified as a complication of MCKD. We herein report a rare case of sporadic MCKD with idiopathic nodular glomerulosclerosis.

Nicotinic acetylcholine receptor agonist reduces acute lung injury after renal ischemia-reperfusion injury by acting on splenic macrophages in mice.

Acute kidney injury (AKI) contributes to the development of acute lung injury (ALI) via proinflammatory responses. We hypothesized that activation of a nicotinic acetylcholine receptor (nAChR), which exerts cholinergic anti-inflammatory effects on macrophages, could reduce ALI after AKI. We aimed to determine whether nAChR agonists could reduce ALI after AKI and which macrophages in the lung or spleen contribute to the improvement of ALI by nAChR agonists. We induced AKI in male mice by unilateral ischemia-reperfusion injury (IRI) with contralateral nephrectomy and administered nAChR agonists in three experimental settings: 1) splenectomy, 2) deletion of splenic macrophages and systemic mononuclear phagocytes via intravenous administration of clodronate liposomes, and 3) alveolar macrophage deletion via intratracheal administration of clodronate liposomes. Treatment with GTS-21, an α7nAChR-selective agonist, significantly reduced the levels of circulating IL-6, a key proinflammatory cytokine, and lung chemokine (C-X-C motif) ligand (CXCL)1 and CXCL2 and neutrophil infiltration, and Evans blue dye (EBD) vascular leakage increased after renal IRI. In splenectomized mice, GTS-21 did not reduce circulating IL-6 and lung CXCL1 and CXCL2 levels and neutrophil infiltration, and EBD vascular leakage increased after renal IRI. In mice depleted of splenic macrophages and systemic mononuclear phagocytes, GTS-21 treatment did not reduce lung neutrophil infiltration, and EBD vascular leakage increased after renal IRI. In mice depleted of alveolar macrophages, GTS-21 treatment significantly reduced lung neutrophil infiltration, and EBD vascular leakage increased after renal IRI. Our findings show that nAChR agonist reduces circulating IL-6 levels and acute lung injury after renal IRI by acting on splenic macrophages.NEW & NOTEWORTHY Acute lung injury associated with acute kidney injury contributes to high mortality. This study showed, for the first time, that nicotinic acetylcholine receptor agonists reduced circulating IL-6 and ALI after renal ischemia-reperfusion injury in mice. These effects of α7nAChR agonist were eliminated in both splenectomized and splenic macrophage (including systemic mononuclear phagocyte)-depleted mice but not alveolar macrophage-depleted mice. nAChR agonist could reduce ALI after AKI via splenic macrophages and provide a novel strategy in AKI.

A case of hypertensive disorders of pregnancy that developed at 9 weeks of gestation.

Preeclampsia and superimposed preeclampsia usually develop after 20 weeks of gestation. We report a case of a 35-year-old Japanese woman who developed hypertensive disorders of pregnancy (HDP) before 20 weeks of gestation. She presented with hypertension and proteinuria at 9 and 11 weeks of gestation, respectively, and developed nephrotic syndrome at 17 weeks of gestation. She did not have definite hypertension or urinary abnormalities before pregnancy. The patient was serologically positive for the antinuclear antibody. However, the complement levels were normal and anti-phospholipid antibody was not detected. A renal biopsy performed at 18 weeks of gestation showed diffuse endotheliosis and tip lesions of secondary focal segmental glomerulosclerosis but no hypertensive changes of the arterioles. Although electron microscopic examination showed electron-dense deposits in the subendothelial lesions, they were considered nonspecific plasma exudation by mass spectrometry. An abortion was performed at 20 weeks gestation because the patient's congestive symptoms due to nephrotic syndrome had worsened and marked fetal growth restriction was observed. After delivery, the patient's symptoms resolved immediately without any additional treatment; however, continuous antihypertensive medication was required. Finally, the patient was diagnosed with HDP based on the renal biopsy findings and her clinical course after delivery. Compared to previous reports, this case describes the earliest onset of HDP. Thus, HDP should be considered as a differential diagnosis in pregnant women with hypertension or proteinuria presenting with symptoms before 20 weeks of gestation.

A Case of Recurrent Atypical Anti-Glomerular Basement Membrane Nephritis Suspicion after Renal Transplantation.

Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM antibody but show linear glomerular basement membrane staining for immunoglobulin. We present a 69-year-old man who underwent a living-donor kidney transplant. The aetiology of the renal failure was a focal segmental glomerulonephritis-like lesion resistant to immunosuppressive therapy. A renal graft biopsy revealed diffuse endocapillary hypercellularity, and mild mesangiolysis with linear GBM staining for IgG. The patient was diagnosed with atypical anti-GBM nephritis since the patient tested negative for circulating anti-GBM antibodies. Treatment involved intravenous methylprednisolone, plasma exchange, and rituximab administration. Protocol graft biopsy performed 1 year after the renal transplant showed a focal segmental glomerulonephritis-like lesion possibly progressing from endocapillary hypercellularity and mesangiolysis. These findings were similar to his native kidney biopsy findings. Although classical recurrent anti-GBM nephritis is rare when a renal transplant is performed after decreased disease activity, this case was considered as a case of recurrent atypical anti-GBM nephritis after renal transplant.

Regular exercise and branched-chain amino acids prevent ischemic acute kidney injury-related muscle wasting in mice.

Acute kidney injury (AKI) causes glucose and protein metabolism abnormalities that result in muscle wasting, thereby affecting the long-term prognosis of critical illness survivors. Here, we examined whether early intervention with treadmill exercise and branched-chain amino acids (BCAA) can prevent AKI-related muscle wasting and reduced physical performance in mice. Unilateral 15 min ischemia-reperfusion injury was induced in contralateral nephrectomized mice, and muscle histological and physiological changes were assessed and compared with those of pair-fed control mice, since AKI causes severe anorexia. Mice exercised for 30 min each day and received oral BCAA for 7 days after AKI insult. By day 7, ischemic AKI significantly decreased wet weight, myofiber cross-sectional area, and central mitochondrial volume density of the anterior tibialis muscle, and significantly reduced maximal exercise time. Regular exercise and BCAA prevented AKI-related muscle wasting and low physical performance by suppressing myostatin and atrogin-1 mRNA upregulation, and restoring reduced phosphorylated Akt and PGC-1α mRNA expression in the muscle. Ischemic AKI induces muscle wasting by accelerating muscle protein degradation and reducing protein synthesis; however, we found that regular exercise and BCAA prevented AKI-related muscle wasting without worsening kidney damage, suggesting that early rehabilitation with nutritional support could prevent AKI-related muscle wasting.

Case report: increased single-nephron estimated glomerular filtration rate in an adult patient with low birth weight.

BACKGROUND: Low birth weight (LBW) is associated with end-stage kidney disease and hypertension and is considered to be a surrogate marker of low nephron number. Low nephron number is hypothesized to contribute to glomerular hyperfiltration that may cause kidney injury; however, this is not yet proven. Until now, the hyperfiltration in LBW patients has not been shown directly yet. CASE PRESENTATION: A 23-years-old female was referred with the persistent proteinuria and decreased renal function (estimated glomerular filtration rate by cystatin C (eGFRcys); 41.86 ml/min). She was a premature baby with low birth weight (704 g, 24 gestational weeks). Renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS) of the perihilar variant with expanded glomerular diameter. We calculated the single-nephron estimated glomerular filtration rate (SN-eGFR) that was higher than that of the same age group in the healthy living kidney donors and speculated that glomerular hyperfiltration is a pathophysiological cause of FSGS. CONCLUSION: This is the first case of SN-eGFR measurement in a patient with LBW. The increased SN-eGFR in this case provides an important insight into the pathophysiological mechanisms of LBW for its progression to kidney disease.

Monoclonal immunoglobulin G1 κ-type atypical antiglomerular basement membrane disease accompanied by necrotizing glomerulonephritis
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INTRODUCTION: Patients without detectable serum antiglomerular basement membrane (GBM) antibodies but with GBM staining for immunoglobulins (Ig), absence of a crescentic phenotype, mild renal insufficiency, and absence of pulmonary hemorrhage have atypical anti-GBM diseases. We report the case of a 64-year-old man with slowly progressive glomerulonephritis. CASE HISTORY: A 64-year-old Peruvian man presented with persistent microscopic hematuria, proteinuria of 2.1 g/g creatinine (Cr), serum Cr 1.00 mg/dL, and C-reactive protein 0.80 mg/dL. Renal biopsy revealed necrotizing glomerulonephritis with 39% cellular crescent formation and diffuse segmental endocapillary proliferation. He had linear staining of monoclonal IgG1-κ in the capillary walls but no detectable serum anti-GBM antibodies. Because renal dysfunction was slowly progressing, steroid monotherapy was initiated, and serum Cr level decreased from 1.48 to 1.13 mg/dL. However, serum Cr increased again to 1.35 mg/dL owing to active glomerular damage with crescent formation and endocapillary proliferation, confirmed by the second renal biopsy at 9 months after therapy. Renal function improved after cyclophosphamide therapy. CONCLUSION: We described an atypical variant of anti-GBM disease due to monoclonal IgG1-κ. Unlike usual atypical anti-GBM disease cases, we observed crescent formation in our patient. Further investigations are needed to identify the cause of nondetectable serum anti-GBM antibodies and to describe the causal relationships between clinicopathological features and the pattern of IgG subclass and light chain in atypical anti-GBM disease.

The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

Objective Urinary angiotensinogen (AGT) is a surrogate marker for intrarenal renin-angiotensin system (RAS) activity that plays an important role in the development of renal damage. Urinary AGT levels are determined by the filtration of plasma AGT through the damaged glomeruli and production of AGT in the proximal tubules. However, the relative merits of the filtration and production of urinary AGT levels in chronic kidney diseases (CKD) have not been clarified. Therefore, we investigated them in CKD patients. Methods We recruited 41 biopsy-proven patients diagnosed with IgA nephropathy (IgAN) in 31, membranous nephropathy (MN) in 5, and tubulointerstitial nephritis (TIN) in 5. The patients taking RAS blockers were excluded. Results The urinary albumin levels in MN patients were significantly higher and those in TIN patients significantly lower than in IgAN patients, and the urinary AGT levels in the MN and TIN patients were significantly higher than those in IgAN patients. Conversely, the urinary AGT-to-urinary albumin (urinary AGT/Alb) ratios were the same for IgAN and MN patients, and those of TIN patients were significantly higher than those of IgAN and MN patients. A multiple linear regression analysis revealed that the urinary AGT/Alb ratios had a significant positive association with IgAN and TIN after adjustments (ß=0.75, and p<0.01). Conclusion These data suggest that the origins of urinary AGT may differ according to the etiology of renal damage [i.e. glomerular damage (such as IgAN and MN) or tubulointerstitial damage (such as TIN)], and a higher urinary AGT/Alb ratio, as in TIN, may reflect AGT production in the kidney.

A case report of thin basement membrane nephropathy accompanied by sporadic glomerulocystic kidney disease.

BACKGROUND: Thin basement membrane nephropathy (TBMN) is a relatively common disease. Patients typically present with isolated hematuria, which has a good renal prognosis. In contrast, glomerulocystic kidney disease (GCKD) is a rare disease, associated with slow progressive renal dysfunction. To our knowledge, co-occurring diagnosis of TBMN with GCKD has not been reported previously. CASE PRESENTATION: A 30-year old woman was admitted to our hospital for evaluation of hematuria and renal insufficiency. Upon examination, her urinary protein level was 40 mg/day and occult blood in her urine was 2+. The patient's urinary dysmorphic red blood cell sediment was 30-49/high power field. In contrast, her serum creatinine levels increased from 0.57 mg/dl to 0.86 mg/dl during the previous 2-years, without special events. She suffered from far-sightedness and astigmatism beginning at birth; She had no family history of renal disease. Renal biopsy demonstrated cystic dilatation of the Bowman's capsule and atrophy of the glomerular tuft. The glomerular basement membrane (GBM) was thin, with an average thickness of 191 nm. Next-generation sequencing was used to evaluate for mutations in COL4A3 and COL4A4, associated with TBMN, and UMOD, MUC1, and SEC61A1, associated with hereditary GCKD. No pathogenic mutations were identified. We thus diagnosed the patient with TBMN coexistent with sporadic GCKD. CONCLUSION: We report the patient diagnosed with TBMN accompanied by sporadic GCKD, based on renal biopsy and genetic testing. Because it is possible that other diseases, such as GCKD, can coexist with TBMN, it is important to consider renal biopsy.

A Rare Case of Lupus Nephritis Presenting as Thrombotic Microangiopathy with Diffuse Pseudotubulization Possibly Caused by Atypical Hemolytic Uremic Syndrome.

A 31-year-old woman was admitted to our hospital for thrombotic microangiopathy (TMA). She was diagnosed with systemic lupus erythematosus (SLE) and class V lupus nephritis. She had no aggravated SLE activity, Shiga toxin positivity, ADAMTS13 abnormality, or other causes of secondary TMA. Plasma exchange partially improved TMA, and eculizumab was introduced for suspected atypical hemolytic uremic syndrome (aHUS), as eculizumab was effective in suppressing the TMA activity. A kidney biopsy revealed diffusely organized crescents (pseudotubulization) with glomerular and arteriolar endothelial injury and subepithelial immune deposits. Thus, this was a rare case of lupus nephritis presenting as TMA with pseudotubulization possibly caused by aHUS.

The Sequential Development of Antiglomerular Basement Membrane Nephritis and Myeloperoxidase-antineutrophil Cytoplasmic Antibody-associated Vasculitis.

A 55-year-old woman presented with deafness, increased levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA), and renal insufficiency with proteinuria and hematuria. Renal biopsy revealed crescentic glomerulonephritis with the linear deposition of immunoglobulin G along the glomerular basement membrane (GBM) and peritubular capillaritis. The anti-GBM antibody levels on admission and 10 days after admission were 11.7 U/mL and 127 U/mL, respectively. These results indicated the sequential development of anti-GBM nephritis and MPO-ANCA-associated vasculitis. This report shows that anti-GBM nephritis may be caused by MPO-ANCA-associated vasculitis because of preceding otitis media, the sequential anti-GBM antibody titers, and the findings of peritubular capillaritis.

Focal segmental glomerulosclerosis associated with cutaneous and systemic plasmacytosis.

Cutaneous and systemic plasmacytosis (CSP) is a rare lymphoproliferative disorder that mainly affects middle-aged Asian individuals. Although Castleman disease is often complicated with various renal involvements, glomerulonephritis associated with CSP, which is considered as a variant of Castleman disease, is rare. This report presents the case of a 41-year-old Japanese man with nephrotic syndrome associated with CSP. Renal biopsy findings showed focal segmental glomerulosclerosis (FSGS) and diffusely mild segmental mesangial proliferation. Plasma cell infiltration in the interstitium was not observed. Electron microscopic findings showed diffuse foot process effacement, localized involvement of subendothelial space widening with amorphous materials, and endothelial cell swelling. Lymph node biopsy findings denied Castleman disease. His skin regions and proteinuria were successfully treated with prednisolone and cyclosporine. The causal relationship between CSP and FSGS is unknown. However, increased serum levels of IL-6 and VEGF and decreased VEGF expression in the podocyte may contribute to renal lesions in patients with CSP. To our best knowledge, this is the first case of a patient with FSGS associated with CSP.

Membranous Nephropathy with an Enhanced Granular Expression of Thrombospondin Type-1 Domain-containing 7A in a Pregnant Woman.

A 30-year-old woman with proteinuria first noted at 26 weeks of gestation was admitted to undergo further evaluation. A renal biopsy revealed membranous nephropathy (MN). There was no evidence of any secondary MN. Prednisolone was initiated 6 months after delivery. Four months later, her urine protein became negative. Enhanced granular staining for thrombospondin type-1 domain-containing 7A (THSD7A) in the glomeruli was retrospectively detected in a biopsy specimen. A literature review revealed that 60% of cases of THSD7A-related MN occurred in women of childbearing age. Therefore, THSD7A-related MN should be considered in female patients presenting with idiopathic MN in childbearing age.

Tubulointerstitial Nephritis Caused by Peritubular Capillaritis Accompanied by Cryoglobulinemia.

A 73-year-old man with fever, renal insufficiency, and purpura was referred to our hospital to be evaluated for renal insufficiency. Renal biopsy revealed acute and chronic tubulointerstitial nephritis with no laboratory findings of sarcoidosis or connective tissue disease. Low C4 levels and elevation of rheumatoid factors suggested cryoglobulinemia, which was confirmed with quantitative analysis. CD34 staining of kidney tissue revealed peritubular capillaritis. Antineutrophil cytoplasmic antibodies were negative. The etiology of peritubular capillaritis was not clear in our patient; however, it might be associated with cryoglobulinemia because we cannot find any other diseases that could have induced the peritubular capillaritis.

Calcitriol-induced hypercalcemia in a patient with granulomatous mycosis fungoides and end-stage renal disease.

An 86-year-old man, diagnosed as having mycosis fungoides in May 2008 and treated with repeated radiation therapy, was admitted to our hospital for initiation of hemodialysis due to end-stage renal disease (ESRD) in April 2012. On admission, his corrected serum calcium level was 9.3 mg/dL, and his intact parathyroid hormone level was 121.9 pg/mL (normal range 13.9-78.5 pg/mL), indicating secondary hyperparathyroidism due to ESRD. After starting hemodialysis, urinary volume diminished rapidly. The serum calcium level increased (12.7 mg/dL), and the intact parathyroid hormone level was suppressed (< 5 pg/mL), while the 1,25-dihydroxyvitamin D3 (calcitriol) level increased (114 pg/mL, normal range: 20.0-60.0 pg/mL) in June 2012. The possibilities of sarcoidosis and tuberculosis were ruled out. Skin biopsies from tumorous lesions revealed a diagnosis of granulomatous mycosis fungoides. The serum soluble interleukin-2 receptor levels and the degrees of skin lesions went in parallel with the increased serum calcium and calcitriol levels. Therefore, the patient was diagnosed as having calcitriol-induced hypercalcemia possibly associated with granulomatous mycosis fungoides. Granulomatous mycosis fungoides is rare, and its association with calcitriol-induced hypercalcemia has not been reported. Careful attention to calcium metabolism is needed in patients with granulomatous mycosis fungoides, especially in patients with ESRD.

Acquired Fanconi syndrome in patients with Legionella pneumonia.

BACKGROUND: Hyponatremia is often observed in patients with Legionella pneumonia. However, other electrolyte abnormalities are uncommon and the mechanism remains to be clarified. CASE PRESENTATION: We experienced two male cases of acquired Fanconi syndrome associated with Legionella pneumonia. The laboratory findings at admission showed hypophosphatemia, hypokalemia, hypouricemia and/or hyponatremia. In addition, they had the generalized dysfunction of the renal proximal tubules presenting decreased tubular reabsorption of phosphate (%TRP), increased fractional excretion of potassium (FEK) and uric acid (FEUA), low-molecular-weight proteinuria, panaminoaciduria and glycosuria. Therefore, they were diagnosed as Fanconi syndrome. Treatment for Legionella pneumonia with antibiotics resulted in the improvement of all serum electrolyte abnormalities and normalization of the %TRP, FEK, FEUA, low-molecular-weight proteinuria, panaminoaciduria and glycosuria, suggesting that Legionella pneumophila infection contributed to the pathophysiology of Fanconi syndrome. CONCLUSION: To the best of our knowledge, this is the first report demonstrating Fanconi syndrome associated with Legionella pneumonia.