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.

Association between adrenal function and dialysis vintage in hemodialysis patients.

INTRODUCTION: Adrenal insufficiency in hemodialysis patients is commonly encountered in clinical practice. However, its association with end-stage renal disease is unclear. We investigated the relationship between adrenal function and relevant clinical parameters, focusing on dialysis vintage. METHODS: Altogether, 100 maintenance hemodialysis patients were enrolled (age: 69.8 ± 11.8 years, dialysis vintage: 9.4 ± 9.2 years). Basal serum cortisol levels were measured and their associations with relevant clinical parameters were investigated. Subsequently, hormone stimulation tests were performed to assess adrenal function. RESULTS: Basal serum cortisol significantly decreased with an increase in dialysis vintage (< 10 years, 11.9 ± 3.7 µg/dL; 10-19 years, 10.9 ± 2.9 µg/dL; ≥ 20 years, 9.7 ± 3.8 µg/dL). Basal cortisol was negatively correlated with dry weight, ß2-microglobulin, creatinine, and lymphocyte count and positively correlated with brachial-ankle pulse wave velocity. Significant negative correlations were observed between basal cortisol and dialysis vintage after adjusting for confounding variables in the multivariate analysis. Standard adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) stimulation tests were performed in 17 patients. Seven patients were diagnosed with adrenal insufficiency and all of them had a long dialysis vintage (≥ 10 years). According to the rapid ACTH test, cortisol responses were significantly decreased in patients with long dialysis vintage compared to those with short dialysis vintage (< 10 years). Similar findings were observed in ten patients without adrenal insufficiency. The CRH loading test showed similar tendencies, although the differences were not statistically significant. CONCLUSIONS: Adrenal function decreased with an increase in dialysis vintage. Long-term dialysis patients might be susceptible to adrenal insufficiency.

IL-17A activated by Toll-like receptor 9 contributes to the development of septic acute kidney injury.

Toll-like receptor 9 (TLR9), which is activated by endogenously released mtDNA during sepsis, contributes to the development of polymicrobial septic acute kidney injury (AKI). However, downstream factors of TLR9 to AKI remain unknown. We hypothesized that IL-17A activated by TLR9 may play a critical role in septic AKI development. To determine the effects of TLR9 on IL-17A production in septic AKI, we used a cecal ligation and puncture (CLP) model in Tlr9 knockout (Tlr9KO) mice and wild-type (WT) littermates. We also investigated the pathway from TLR9 activation in dendritic cells (DCs) to IL-17A production by γδT cells in vitro. To elucidate the effects of IL-17A on septic AKI, Il-17a knockout (Il-17aKO) mice and WT littermates were subjected to CLP. We further investigated the relationship between the TLR9-IL-17A axis and septic AKI by intravenously administering recombinant IL-17A or vehicle into Tlr9KO mice and assessing kidney function. IL-17A levels in both plasma and the peritoneal cavity and mRNA levels of IL-23 in the spleen were significantly higher in WT mice after CLP than in Tlr9KO mice. Bone marrow-derived DCs activated by TLR9 induced IL-23 and consequently promoted IL-17A production in γδT cells in vitro. Knockout of Il-17a improved survival, functional and morphological aspects of AKI, and splenic apoptosis after CLP. Exogenous IL-17A administration aggravated CLP-induced AKI attenuated by knockout of Tlr9. TLR9 in DCs mediated IL-17A production in γδT cells during sepsis and contributed to the development of septic AKI.

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.

Sodium-Glucose Cotransporter-2 Inhibitor Immediately Decreases Serum Uric Acid Levels in Type 2 Diabetic Patients.

BACKGROUND Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new antihyperglycemic drugs for type 2 diabetes. SGLT2 inhibitors ameliorate cardiovascular morbidity and mortality as well as kidney disease progression by reducing body weight (BW), blood pressure (BP), visceral adiposity, albuminuria, and serum uric acid and blood glucose levels. However, it is not clear which effects are pronounced, and what mechanisms are associated with these effects. MATERIAL AND METHODS This study recruited patients with type 2 diabetes who were prescribed an SGLT2 inhibitor for the first time in our outpatient department. Clinical parameters were measured before and 6 months after the administration of the SGLT2 inhibitor, without the addition of new drugs and dose changes for all prescribed drugs. RESULTS This study recruited 24 patients with type 2 diabetes. No significant differences in BP, glycated hemoglobin (HbA1c) levels, and low-density lipoprotein cholesterol levels were observed after SGLT2 inhibitor administration. In contrast, BW and serum uric acid levels decreased significantly, and the fractional excretion of uric acid (FEUA) increased significantly after administration. While no significant relationships were observed between serum uric acid and FEUA with respect to the percentage changes from baseline values, the percentage changes in serum uric acid levels from baseline were significantly and positively associated with those in serum creatinine levels. CONCLUSIONS Serum uric acid levels were immediately decreased owing to the administration of SGLT2 inhibitor, but BP, blood glucose, and serum lipid levels were unchanged. These changes in serum uric acid levels may be associated with changes in renal function.

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.

Increased heart rate is associated with intrarenal renin-angiotensin system activation in chronic kidney disease patients.

BACKGROUND: A higher heart rate is one of the risk factors for heart failure and cardiovascular disease. Activation of the intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. However, the association between heart rate and intrarenal RAS activation is unclear. METHODS: We investigated the relationship between heart rate and urinary angiotensinogen (U-AGT) excretion, a surrogate marker for intrarenal RAS activity, in ten subjects without chronic kidney disease (CKD) and 72 CKD patients who were not taking medications that influence heart rate and RAS blockers (age 50.0 ± 17.4 years, 27 men and 45 women, serum creatinine (sCr) 1.85 ± 2.71 mg/dL, blood pressure 120.5 ± 15.8/72.9 ± 10.1 mmHg, heart rate 67.3 ± 8.9 /min, urinary protein excretion 1.27 ± 2.63 g/day, and U-AGT excretion 747.4 ± 2714.6 µg/day). RESULTS: As heart rate is influenced by behavior and emotion, we divided it into daytime and nighttime. Heart rate had a significant positive association with sCr levels during daytime and nighttime in CKD patients but not in non-CKD subjects. Moreover, although heart rate was not associated with U-AGT excretion levels in non-CKD subjects, it was associated with U-AGT excretion levels during daytime (r = 0.23 and p = 0.047) and nighttime (r = 0.45 and p < 0.01) in CKD patients. Multiple linear regression analysis revealed that heart rate had a significant positive association with the U-AGT excretion levels during nighttime, but not daytime, after adjustments for age, sex, body mass index, and sCr (ß = 0.31 and p = 0.034). CONCLUSION: Heart rate is associated with U-AGT excretion levels, especially during the nighttime, in CKD patients.

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.

Melatonin ameliorates intrarenal renin-angiotensin system in a 5/6 nephrectomy rat model.

BACKGROUND: Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. It has been reported that reactive oxygen species (ROS) are important components of intrarenal RAS activation. Melatonin is recognized as a powerful antioxidant, and we recently reported that impaired nighttime melatonin secretion correlates negatively with urinary angiotensinogen excretion, the surrogate marker of intrarenal RAS activity in patients with CKD. However, whether melatonin supplementation ameliorates the augmentation of intrarenal RAS in CKD has remained unknown. We aimed to clarify whether exogenous melatonin ameliorates intrarenal RAS activation via the reduction of ROS production. METHODS: 5/6 Nephrectomized (Nx) rats were used as a chronic progressive CKD model and compared with sham-operated control rats. The Nx rats were divided into untreated Nx rats and melatonin-treated Nx rats. The levels of intrarenal RAS, ROS components, and renal injury were evaluated after 4 weeks of treatment. RESULTS: Compared with the control rats, the untreated Nx rats exhibited significant increases in intrarenal angiotensinogen, angiotensin II (AngII) type 1 receptors, and AngII, accompanied by elevated blood pressure, higher oxidative stress (8-hydroxy-2'-deoxyguanosine), lower antioxidant (superoxide dismutase) activity, and increased markers of interstitial fibrosis (α-smooth muscle actin, Snail, and type I collagen) in the remnant kidneys. Treatment with melatonin significantly reversed these abnormalities. CONCLUSION: Antioxidant treatment with melatonin was shown to ameliorate intrarenal RAS activation and renal injury in a 5/6 Nx rat model.

Acquired resistance to rechallenge injury after acute kidney injury in rats is associated with cell cycle arrest in proximal tubule cells.

Rats that have recovered from severe proximal tubule (PT) injury induced by uranyl acetate (UA), a toxic stimulus, developed resistance to subsequent UA treatment. We investigated cell cycle status and progression in PT cells in relation to this acquired resistance. Fourteen days after pretreatment with saline (vehicle group) or UA [acute kidney injury (AKI) group], rats were injected with UA or lead acetate (a proliferative stimulus). Cell cycle status (G0/G1/S/G2/M) was analyzed by flow cytometry. The expression of cell cycle markers, cyclin-dependent kinase inhibitors, and phenotypic markers were examined by immunohistochemistry. Cell cycle status in PT cells in the AKI group was comparable to those of the vehicle group. However, more early G1-phase cells (cyclin D1- or Ki67-) and p21+ or p27+ cells were found in the PT of the AKI group than in that of the vehicle group. UA induced G1 arrest and inhibited S phase progression with earlier dedifferentiation and less apoptosis in PT cells of the AKI group. Lead acetate induced proliferation without dedifferentiation but with delayed G0-G1 transition and inhibited S phase progression in PT cells in the AKI group. Sustained p21 and increased p27 expression in PT cells were found in the AKI group in response to UA and lead acetate. PT cells in the AKI group inhibited cell cycle progression by enhanced G1 arrest, probably via p21/p27 modulation as an injury or proliferation response, resulting in cytoresistance to rechallenge injury.

Disturbed circadian rhythm of the intrarenal renin-angiotensin system: relevant to nocturnal hypertension and renal damage.

BACKGROUND: The intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. Disruption of diurnal blood pressure (BP) variation is an additional risk factor for renal damage. However, little is known regarding whether intrarenal RAS circadian rhythm exists or if it influences the disruption of diurnal BP and renal damage. METHODS: We investigated the circadian rhythm of urinary angiotensinogen (U-AGT) that reflects intrarenal RAS activity in 14 individuals without chronic kidney disease (CKD) and 36 CKD patients classified according to circadian BP rhythms. RESULTS: BP values were higher during the daytime than during the nighttime in both individuals without CKD and CKD patients. U-AGT levels were not different between the daytime and nighttime in individuals without CKD, but were significantly higher in the daytime in CKD patients (log U-AGT/creatinine: daytime, 2.39 ± 0.99; nighttime, 2.24 ± 1.06; p = 0.001). Furthermore, in CKD patients showing a riser pattern of circadian BP, U-AGT levels did not decrease during the nighttime compared with those in the daytime (log U-AGT/creatinine: daytime, 2.51 ± 0.65; nighttime, 2.52 ± 0.71; p = 0.78). Circadian fluctuation of albuminuria and proteinuria occurred parallel to that of the U-AGT levels. U-AGT levels were significantly and positively correlated with the levels of BP and circadian fluctuation of U-AGT was correlated with diurnal BP changes. CONCLUSION: These data suggest that the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which are associated with diurnal BP variation.

The level of urinary α1 microglobulin excretion is a useful marker of peritubular capillaritis in antineutrophil cytoplasmic antibody associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis affects small vessels in the kidney (i.e., arterioles, glomerular or peritubular capillaries, or venules). Although crescentic glomerulonephritis is a common histological finding, the incidence of peritubular capillaritis (PTC) or arteriolitis is unclear. Moreover, the laboratory data that reflect the degree of renal histological damage and distinguish between PTC and arteriolitis have not yet been clarified. METHODS: We investigated laboratory data and histological findings from 11 patients diagnosed with ANCA-associated vasculitis (2 men and 9 women, mean age 70.3 ± 3.3 years) whose renal biopsies were performed between 2009 and 2014. RESULTS: All patients were positive for myeloperoxidase (MPO)-ANCA. PTC or arteriolitis was detected in six patients (54.5 %), respectively. The only significant positive relationship between laboratory data and histological findings observed was that between levels of urinary α1 microglobulin (u-α1MG) excretion and the percentage of tubular atrophy and interstitial fibrosis (r = 0.67, p = 0.035). No significant differences in laboratory data were found between patients with or without arteriolitis. However, the levels of u-α1MG excretion were significantly higher in patients with PTC than in those without PTC (75.2 ± 19.5 vs. 15.0 ± 3.6 mg/dl, p = 0.035). CONCLUSION: PTC or arteriolitis occurs at a high rate independently of crescentic glomerulonephritis in ANCA-associated vasculitis patients. The levels of u-α1MG excretion reflect the degrees of tubular atrophy and interstitial fibrosis. Moreover, high levels of u-α1MG excretion suggest that PTC is more likely than arteriolitis in ANCA-associated vasculitis patients.

Alogliptin improves steroid-induced hyperglycemia in treatment-naïve Japanese patients with chronic kidney disease by decrease of plasma glucagon levels.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for end-stage renal failure and cardiovascular disease, and a strategy to counteract CKD must be established. CKD caused by immunological abnormalities is treated by steroids, frequently resulting in steroid diabetes. Although insulin is the most effective drug against steroid diabetes, administering it to patients can be difficult. Dipeptidyl peptidase-4 (DPP-4) inhibitors were developed for diabetes mellitus with a new mechanism of action. However, their efficacies and mechanisms of action for steroid diabetes are unclear. MATERIAL AND METHODS: We studied 11 CKD patients treated with steroids admitted to our hospital (3 men and 8 women; age, 66.0 ± 15.9 years). DPP-4 inhibitor alogliptin was administered for steroid diabetes. Levels of markers related to glucose metabolism were measured before alogliptin treatment and after alogliptin treatment, before the prednisolone dose was reduced. RESULTS: Alogliptin treatment significantly increased plasma glucagon-like peptide-1 (GLP-1) levels from 1.16 ± 1.71 pmol/L to 4.48 ± 1.53 pmol/L and significantly reduced levels of plasma glucose recorded 2 h after lunch and hemoglobin A1c (HbA1c). No significant differences were seen in insulin secretory ability of homeostasis model assessment (HOMA) (HOMA-ß) and insulin resistance index of HOMA (HOMA-R) before and after alogliptin treatment. In contrast, alogliptin treatment significantly decreased plasma glucagon levels, from 116.1 ± 38.7 pg/mL to 89.6 ± 17.3 pg/mL. Moreover, there were significant correlations among HbA1c, GLP-1, and glucagon levels. CONCLUSIONS: Alogliptin improves steroid-induced hyperglycemia by decrease of glucagon levels through an increase in plasma GLP-1 levels.

Teriparatide-Associated Hypercalcemia Concomitant With Acute Kidney Injury: A Case-Report.

Teriparatide, a recombinant human parathyroid hormone, is an anabolic treatment for osteoporosis with a high risk of fractures. Transient hypercalcemia is an adverse effect of teriparatide and usually resolves within 16h of teriparatide administration owing to its rapid absorption and elimination. Some cases of prolonged hypercalcemia have been reported, but these improved rapidly after teriparatide discontinuation. Here, we describe a rare case of teriparatide-induced hypercalcemia concomitant with acute kidney injury that persisted for four weeks. An 83-year-old woman began taking teriparatide for a vertebral fracture. The patient was immobilized by the fracture. Three weeks later, the patient developed hypercalcemia and acute kidney injury. However, hypercalcemia persisted for four weeks despite the discontinuation of teriparatide and fluid administration. Clinicians should be aware that teriparatide can induce severe hypercalcemia, especially in the setting of immobilization, and that hypercalcemia can persist for more than 3-4 weeks in patients with decreased kidney function.

Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study.

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

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.

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.

Relationship between urinary fractional excretion of sodium and life prognosis in liver cirrhosis patients.

AIM: Renal vasoconstriction in generalized vasodilatation with blood pooling and the consequent reduction in effective arterial volume is the pathophysiological basis of liver cirrhosis (LC). Low levels of fractional excretion of sodium (FENa) are an effective marker of hypoperfusion of the renal artery. However, the relationship between levels of FENa, LC severity and life prognosis has not yet been elucidated. METHODS: We examined 57 LC patients (39 men and 18 women; mean age, 70.5 ± 8.8 years; underlying liver disease, type B hepatitis in eight patients, type C hepatitis in 37, alcoholic hepatitis in four and others in eight) with renal dysfunction (estimated glomerular filtration rate (eGFR) <60 mL/min) who were admitted to our hospital. RESULTS: Nine patients died because of uremia, liver failure, gastrointestinal bleeding and infection. No differences were found in patient background and blood pressure. However, in addition to differences in the levels of aspartate aminotransferase (AST), cholinesterase, albumin, prothrombin time (PT), eGFR and Model for End-Stage Liver Disease (MELD) score, the patients who died had significant differences in levels of FENa. The levels of FENa were significantly and inversely correlated with blood urea nitrogen, total bilirubin, AST, Child-Pugh score and MELD score, and were significantly and positively correlated with cholinesterase, albumin and PT. Moreover, the sensitivity (88%) and specificity (93%) of the levels of FENa of less than 0.4% to predict death were remarkably high. CONCLUSION: Levels of FENa may reflect LC severity and may be associated with the life prognosis of LC patients.