Search

Purpose To report the endovascular treatment for acute progressive and very-late-onset multiple segmental small-artery stenoses in transplanted kidney parenchyma presenting with rapidly deteriorating renal function and refractory hypertension in a 65-year-old man. Case report Nineteen years ago, the patient received a living renal transplant via end-to-end anastomosis of the right internal iliac artery for kidney failure caused by chronic glomerulonephritis. His transplant renal function (creatinine: 0.9 mg/dL) and blood pressure were stable for 18 years. Then rapid worsening of renal function (creatinine: 2.5 mg/dL) and refractory hypertension occurred. Magnetic resonance angiography and renal angiography showed multiple small segmental artery stenoses in the transplanted kidney. At the 1-month follow-up consultation, total occlusion of 2 branches traversing the inferior pole of the kidney was observed, revealing acute progression of artery stenosis. Balloon angioplasty was successfully performed on those branches; renal function improved (creatinine: 1.3 mg/dL), and blood pressure was sufficiently controlled. Conclusions This is a rare case that revealed very-late-onset multiple segmental renal artery stenoses with acute progression in the transplant kidney. Even multiple small segmental artery stenoses can reduce transplant renal function in the chronic phase and progress rapidly. Early percutaneous transluminal angioplasty may thus be feasible and important for preventing graft loss.

A 75-year-old man with fever was diagnosed with alveolar hemorrhage. Antineutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3 were absent. He received corticosteroid therapy, which immediately improved his symptoms and chest radiological findings. After the discontinuation of corticosteroids, fever and general fatigue relapsed, and renal function deteriorated with hematuria and proteinuria. A nerve conduction study revealed mononeuritis multiplex. Renal biopsy demonstrated focal necrotizing crescentic glomerulonephritis with endocapillary proliferative lesions, immunofluorescence C3 deposits, and electron-microscopic subepithelial hump-like deposits. Nephritis-associated plasmin receptor (NAPlr) and plasmin activity, biomarkers of infection-related glomerulonephritis, were positive in glomeruli. Although pathological findings suggested infection-related glomerulonephritis (IRGN), clinical manifestations, such as alveolar hemorrhage and mononeuritis multiplex, suggested systemic small vessel vasculitis. After corticosteroid therapy, systemic symptoms disappeared, and the gradual amelioration of hematuria and proteinuria was observed. Based on the clinical symptoms for which steroid therapy was effective, the patient was considered to have systemic small vessel vasculitis, the etiology of which may have been associated with infection.

Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.

Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.

Dietary salt restriction is essential for managing fluid retention in patients with chronic kidney disease (CKD). In this retrospective cohort study, we investigated weight loss from the perspective of fluid status in CKD patients during a 7-day hospitalization period while consuming a low-salt diet (5 g/day). Among 311 patients, the median weight loss (interquartile range, maximum) was 0.7 (0.0–1.4, 4.7) kg on Day 4 and 1.0 (0.3–1.7, 5.9) kg on Day 7. Patients were classified into quartiles based on pre-hospital urinary salt excretion (quartile [Q] 1, 1.2–5.7; Q2, 5.8–8.4; Q3, 8.5–11.3; Q4, 11.4–29.2 g/day). Weight loss was significantly greater in Q3 and Q4 than in Q1. The body mass index (BMI) and urinary salt excretion in the first 24 hours after admission were independently associated with rapid weight loss on Day 4 by multivariate logistic regression analysis. In conclusion, CKD patients with a high salt intake or high BMI exhibit rapid weight loss within a few days of consuming a low-salt diet. Dietary salt restriction is effective for reducing proteinuria in these patients, but long-term observation is needed to confirm the sustained effects.

Hyponatremia is a common finding after subarachnoid hemorrhaging (SAH) and can be caused by either cerebral salt-wasting syndrome (CSWS) or syndrome of inappropriate antidiuretic hormone (SIADH). Distinguishing between these two entities can be difficult because they have similar manifestations, including hyponatremia, serum hypo-osmolality, and high urine osmolality. We herein report the case of a 60-year-old man who suffered from SAH complicated by hyponatremia. During his initial hospitalization, he was diagnosed with CSWS. He was readmitted one week later with hyponatremia and was diagnosed with SIADH. This is the first report of SAH causing CSWS followed by SIADH. These two different sources of hyponatremia require different treatments.

A 30-year-old woman with myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplantation (HSCT) derived from her HLA-matched sister six years previously. She received preconditioning total body irradiation with renal shielding and was subsequently administered cyclosporin A (CyA) as prophylaxis against graft-versus-host disease (GVHD). Four months after HSCT, asymptomatic proteinuria and glomerular hematuria developed during CyA tapering without obvious extrarenal involvements of GVHD, and persisted for six years. A renal biopsy revealed endothelial injury in the glomeruli, and the deposition of C4d was detected diffusely on glomerular capillaries and focally on peritubular capillaries, suggesting that nephropathy involved antibody- or complement-associated immune reactions.

Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disease caused by GATA3 mutations. Although several cases with variable renal features have been reported, the presence of histological changes within the glomeruli in adult patients is unclear. We herein report an adult case of HDR syndrome with a novel p.C288W (TGC>TGG) missense mutation in GATA3. His renal histology showed a membranoproliferative glomerulonephritis-like glomerular lesion. Additional renal histological analyses of HDR syndrome patients will be needed to clarify the role of GATA3 in both the developing and adult kidney.

We report the case of a Japanese family suffering from familial juvenile hyperuricemic nephropathy (FJHN) due to a rare missense mutation of the uromodulin (UMOD) gene. An 18-year-old male presented with gout, hyperuricemia, and stage 3 chronic kidney disease. Mostly, FJHN is caused by a mutation altering the cystine residue of UMOD/Tamm-Horsfall protein. However, in the present case, a T688C mutation was identified in exon 4, resulting in amino acid substitution with arginine replacing tryptophan at position 230 (Trp230Arg). This mutation was also found in his brother and father with the same phenotype, indicating autosomal dominant inheritance. The affected amino acid was conserved in 200 healthy Japanese controls. Therefore, mutation T688C most likely causes rare structural and/or functional abnormalities in UMOD/Tamm-Horsfall protein.

Background: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. Methods: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. Results: HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29–25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40–0.74; p < 0.001). Conclusion: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.

症例は68歳，男性．主訴は，全身倦怠感，PD排液異常．既往歴に関節リウマチを認める．現病歴：慢性腎不全（原疾患不明）のためSMAP法にてPDカテーテル挿入．その後2006年10月からCAPDにて当院で透析導入．2年9か月のPD歴で，出口部感染や腹膜炎の既往を認めず経過していた．2009年6月X日にエリスロポエチン注射と採血を実施，特に体調不良の訴えもなく帰宅した．後日判明した採血結果でCRPが31.24mg/dLと異常高値を示していた．その前後に腹痛なく，排液混濁も認めなかったが，同年7月10日早朝より「腹痛はないが，突然に透析液の注入途中から肛門より排液する」との訴えで診察依頼があり，独歩にて救急来院した．PDカテーテルから食物残渣を含む混濁した排液を確認，穿孔性腹膜炎を疑い，緊急開腹手術をした．カテーテル周囲で瘻孔形成し，癒着した消化管の剥離に難渋して穿孔部位の同定は困難であった．臨床経過から本症例の穿孔性腹膜炎の機序は次のとおりと推察する．すなわち，憩室炎などを原因にすでに潜在した腹膜炎を約2週間前に発症し，被覆した腸間膜とカテーテルが治癒過程において癒着．その後，機械的刺激によりCAPDカテーテル先端が脆弱箇所を穿通し，腸管内に迷入した．PD患者の穿孔性腹膜炎の診断はしばしば困難である．その理由に，(1)free airや腹水が消化管穿孔の根拠になりにくいこと，(2)腹膜透析液による洗浄効果で腹膜刺激症状が緩和されること，(3)通常のPD腹膜炎との鑑別が困難であること等があげられ，高い死亡率の原因となっている．穿孔性腹膜炎の死亡率が高いことから臨床上，極めて危険な合併症であるといえる．腹膜透析液による洗浄効果で腹膜刺激症状が緩和されるなど発見が遅れる可能性があることを留意し，排液の詳細な観察ならびに炎症所見などのデータの推移には十分注意する必要があると思われた．

A 70-year-old woman developed anemia and kidney injury 10 months after mitral valve (MV) repair. Serological findings and Doppler echocardiography suggested hemolytic anemia due to mitral regurgitation jet collision with an annuloplasty ring (MRCR). Since kidney injury persisted even without exacerbation of anemia over 10 months, we performed an MV replacement. The anemia improved rapidly after the surgery; however, the renal function remained chronic kidney disease (CKD) after reoperation. Kidney injury was thought to be due to iron deposition and decreased renal perfusion that caused tubular injury. A comprehensive literature review shows that hemolysis due to MRCR in the early postoperative phase (within 3 postoperative months) can be often ameliorated with endothelialization without the need for reoperation; however, hemolysis in the late postoperative phase can persist even for a long period without reoperation. Chronic hemolysis can lead to kidney injury and progress to CKD even without clinical evidence of exacerbation of anemia. Therefore, in cases of late postoperative phase hemolysis, reoperation should be considered for better management of kidney injury and hemolytic anemia.

A 70-year-old woman developed anemia and kidney injury 10 months after mitral valve (MV) repair. Serological findings and Doppler echocardiography suggested hemolytic anemia due to mitral regurgitation jet collision with an annuloplasty ring (MRCR). Since kidney injury persisted even without exacerbation of anemia over 10 months, we performed an MV replacement. The anemia improved rapidly after the surgery; however, the renal function remained chronic kidney disease (CKD) after reoperation. Kidney injury was thought to be due to iron deposition and decreased renal perfusion that caused tubular injury. A comprehensive literature review shows that hemolysis due to MRCR in the early postoperative phase (within 3 postoperative months) can be often ameliorated with endothelialization without the need for reoperation; however, hemolysis in the late postoperative phase can persist even for a long period without reoperation. Chronic hemolysis can lead to kidney injury and progress to CKD even without clinical evidence of exacerbation of anemia. Therefore, in cases of late postoperative phase hemolysis, reoperation should be considered for better management of kidney injury and hemolytic anemia.

A 27-year-old woman was referred to our hospital because of pancytopenia and nephritic syndrome in November, 2008. The findings of physical and laboratory examinations showed systemic lupus erythematosus (SLE). Diffuse proliferative lupus nephritis(group IV-G(A))was confirmed by renal biopsy. After combined therapy with prednisolone, intravenous cyclophosphamide pulse and mizoribine, proteinuria decreased from 13.0 g/day to 2.0 g/day and the serum complement level recovered to the normal level. However, she visited our hospital again for management of bleeding tendency in July 2009. She was diagnosed as hemophagocytic syndrome (HPS), with pancytopenia, high ferritin, high LDH level and hemophagocytosis in the bone marrow. She was treated effectively with steroid pulse therapy, but relapsed with HPS after two weeks. Although her child caught a cold, the case did not show any sign or symptom of infection, such as the common cold. However, we diagnosed her HPS as infection-associated hemophagocytic syndrome (IAHS) because she was not in the active phase of SLE at the onset of hemophagocytosis and the laboratory findings showed elevation of her serum ferritin and LDH. Therefore, we considered that her infectious sign may have been concealed by immunosuppressive therapy with prednisolone for SLE. It is very difficult to distinguish between IAHS and autoimmune-associated hemophagocytic syndrome (AAHS)in autoimmune diseases, but the differential diagnosis is necessary to treat the HPS. Here, we report an important case of HPS complicated with SLE. This case may attract interest particularly in the management of HPS-complicated autoimmune disease. Therefore, we report it with a review of the literature.

OBJECTIVE: This open-label, randomized controlled trial investigated the effects of cilnidipine, an L/N-type calcium channel blocker (CCB), in patients with chronic kidney disease (CKD). METHODS: Sixty patients with CKD and well-controlled hypertension being treated with a renin—angiotensin system (RAS) inhibitor and an L-type CCB (L-CCB) were randomly assigned either to switch from the L-CCB to cilnidipine after a 4-week observation period or to continue with L-CCB treatment. Blood pressure, heart rate and renal function were monitored for 12 months. Data were available for analysis from 50 patients: 24 from the cilnidipine group and 26 from the L-CCB group. RESULTS: Blood pressure was well controlled in both groups. After 12 months, proteinuria and heart rate were significantly decreased in the cilnidipine group, but proteinuria increased and heart rate remained unchanged in the L-CCB group. There was a significant positive correlation between the percentage changes in proteinuria and heart rate. CONCLUSIONS: Cilnidipine has antihypertensive effects equivalent to those of L-CCBs. In patients with CKD, proteinuria can be decreased by switching from an L-CCB to cilnidipine, thereby improving renal function.

Atherosclerotic cardiovascular disease (CVD) is a significant cause of morbidity and mortality in patients with chronic kidney disease (CKD), particularly patients undergoing hemodialysis (HD). The death rate from CVD in patients with advanced stage CKD is 10 to 40 times higher than that in the general population (Iliou et al., 2001; Sarnak et al., 2003). A majority of patients with CKD have traditional CVD risk factors such as old age, diabetes mellitus, systolic hypertension, smoking, and dyslipidemia. However, the interventions to address these traditional risk factors have failed to decrease the risk for CVD in patients with CKD (Stenvinkel et al., 2008). Atherosclerotic lesions develop through chronic inflammatory processes, and chronic inflammation is a common feature of CKD. In addition, the metabolic milieu during the development of renal dysfunction appears to accelerate the atherosclerotic process by decades in patients with CKD. Given these findings, many researchers have emphasized that nontraditional risk factors such as oxidative stress and advanced glycation endproducts (AGEs), in combination with their receptor (RAGE), may play an important role in the development of CVD in patients with CKD. RAGE is a member of the immunoglobulin superfamily of cell surface molecules. Enhanced RAGE expression has been observed in peripheral blood monocytes of patients with CKD, suggesting that RAGE may amplify ligand-induced monocyte perturbation and contribute to monocyte-mediated vascular inflammation in patients with CKD. The major alteration of glycated protein in patients with CKD is decreased clearance of glycation-free adducts and their markedly increased levels in plasma. However, the change of plasma AGEs into proteins in patients with CKD is relatively modest. Therefore, ligands other than AGEs for RAGE may be more important in RAGE-mediated atherosclerosis of patients with CKD. Several RAGE ligands, including S100 proteins, the High Mobility Group Box proteins, and amyloid fibrils, have been identified. Among them, emerging evidence indicates that S100A12 is a proinflammatory cytokine (Pietzsch and Hoppmann, 2009). In this review, we

Summary Background and objectives S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease. Design, setting, participants, & measurements A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants. Results Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n 197; 33.8 28.1 ng/ml) than in those without it (n 353; 20.2 16.1 ng/ml; P 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P 0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P 0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P 0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n 348). Conclusions These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients. Clin J Am Soc Nephrol 6: ●●● –●●● , 2011. doi: 10.2215/CJN.08310910

Background/Aims: Peritoneal fibrosis leads to discontinuation of peritoneal dialysis. Although aldosterone promotes tissue fibrosis in many organs, its contribution to peritoneal fibrosis and the underlying mechanism are poorly understood. The present study investigated the direct effect of aldosterone on cultured rat peritoneal fibroblasts (RPFs). Methods: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors (MRs), 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), serum- and glucocorticoid-inducible protein kinase 1 (SGK1), and connective tissue growth factor (CTGF) mRNA was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). To determine the role of reactive oxygen species (ROS) induced by aldosterone, an active oxygen assay with several inhibitors was used. The ability of RPFs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA (siRNA) of SGK1 was transfected into cultured cells using lipofectamine. Results: CYP11B2, MRs, and 11β-HSD2 were expressed in RPFs. The release of aldosterone from RPFs into the culture medium was confirmed. Aldosterone increased the expression of SGK1 mRNA via ROS generation. Spironolactone, apocynin, and tempol significantly reduced SGK1 expression. Aldosterone upregulated CTGF transcripts significantly. SGK1 gene silencing suppressed aldosterone-induced CTGF expression. Conclusion: The local aldosterone system acts directly as a profibrotic factor via ROS-mediated SGK1 in RPFs.

Background The pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity. Methods We conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline. Results The study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67). Conclusions Lower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3135-6) contains supplementary material, which is available to authorized users.

Background S100A12 protein is an endogenous receptor ligand for advanced glycation end products. In this study, the plasma S100A12 level was assessed as an independent predictor of mortality, and its utility in clinical settings was examined. Methods In a previous cross-sectional study, plasma S100A12 levels were measured in 550 maintenance hemodialysis patients to determine the association between S100A12 and the prevalence of cardiovascular diseases (CVD). In this prospective study, the risk of mortality within a two-year period was determined. An integer scoring system was developed to predict mortality on the basis of the plasma S100A12 levels. Results Higher plasma S100A12 levels (≥18.79 ng/mL) were more closely associated with higher all-cause mortality than lower plasma S100A12 levels (P = 0.001). Multivariate Cox proportional hazards analysis revealed higher plasma S100A12 levels [hazard ratio (HR), 2.267; 95% confidence interval (CI), 1.195–4.302; P = 0.012], age ≥65 years (HR, 1.961; 95%CI, 1.017–3.781; P = 0.044), serum albumin levels P = 0.012), and history of CVD (HR, 2.068; 95%CI, 1.146–3.732; P = 0.016) to be independent predictors of two-year all-cause mortality. The integer score was derived by assigning points to these factors and determining total scores. The scoring system revealed trends across increasing scores for predicting the all-cause mortality [c-statistic = 0.730 (0.656–0.804)]. The resulting model demonstrated good discriminative power for distinguishing the validation population of 303 hemodialysis patients [c-statistic = 0.721 (0.627–0.815)]. Conclusion The results indicate that plasma S100A12 level is an independent predictor for two-year all-cause mortality. A simple integer scoring system was therefore established for predicting mortality on the basis of plasma S100A12 levels.