Association between serum lipids, polyunsaturated fatty acids, and prognosis in maintenance hemodialysis patients.

INTRODUCTION: Risks of mortality and cardiovascular disease (CVD) are significantly higher in hemodialysis (HD) patients than in the general population, where dyslipidemia is an established risk factor for CVD and mortality. There is no clear conclusion, however, whether dyslipidemia is a significant risk factor for CVD and mortality in HD patients. Similarly, the association between the polyunsaturated fatty acids (PUFAs) and the mortality is not clear in HD patients. METHODS: We retrospectively investigated mortality and CVD events in 420 HD patients. We classified patients into high- and low-lipid groups depending on their lipid levels. Survival rates were calculated using the Kaplan-Meier analysis and evaluated by the log-rank test. The risk estimates were computed using a multivariate Cox proportional hazard analysis. FINDINGS: During their follow-up (June 2011 to June 2016), 151 patients died (37 of CVD), and 112 patients experienced new CVD events. On Kaplan-Meier analysis, the number of all-cause deaths and CVD events were significantly higher in the low HDL-cholesterol group (P < 0.01, log-rank test). Similarly, the number of all-cause deaths was significantly higher in the high eicosapentaenoic acid/arachidonic acid ratio group (P < 0.01, log-rank test). Multivariate Cox proportional analysis showed that HDL-cholesterol was a significant prognostic indicator for new onset of CVD events (low: 0, high: 1, hazard ratio 0.66, 95% confidence interval 0.44-0.97; P = 0.04). DISCUSSION: In HD patients, LDL-cholesterol and non-HDL-cholesterol levels are not associated with mortality or CVD events. The HDL-cholesterol level, however, is an independent predictor of new CVD events even in HD patients.

Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status.

INTRODUCTION: We previously reported that fibroblast growth factor 23 (FGF23)-klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23-klotho signaling pathway in immune cells may occur in these patients. METHODS: We analyzed the number of klotho-positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme-linked immunosorbent assay. RESULTS: The number of klotho-positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients. CONCLUSIONS: We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti-inflammatory and immunosuppressive factor.

Correlation between haemoglobin level and type of erythropoiesis-stimulating agent at initiation of haemodialysis.

Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients with chronic kidney disease is correlated with cardiovascular disease and mortality. Objective This study was performed to determine whether short- and long-acting erythropoiesis-stimulating agents are correlated with the pre-haemodialysis haemoglobin level in patients with chronic kidney disease. Setting This study was conducted at the Blood Purification Center in Wakayama Medical University. Method We enrolled 364 patients undergoing initiation of haemodialysis from January 2009 to June 2015 and analysed them for > 3 months prior to the initiation of haemodialysis. In total, 168 patients were included in the final analysis based on the inclusion and exclusion criteria. Main outcome measures The correlation of the haemoglobin level at the initiation of haemodialysis with various factors according to the type of erythropoiesis-stimulating agent used. Results The median haemoglobin level was 8.8 g/dL, and long-acting erythropoiesis-stimulating agents were used by 69.6% of the patients. Long-acting erythropoiesis-stimulating agents were used significantly more often in patients with high than low haemoglobin levels. The haemoglobin levels at the initiation of haemodialysis and 1 month prior tended to be significantly higher in patients taking long-than short-acting erythropoiesis-stimulating agents. The serum levels of iron and albumin and the use of long-acting erythropoiesis-stimulating agents were independently correlated with the haemoglobin level at the initiation of haemodialysis in the multivariate regression analysis. In addition, the left ventricular mass index was significantly correlated with the haemoglobin level at the initiation of haemodialysis. Conclusion Long-acting erythropoiesis-stimulating agents were correlated with higher haemoglobin levels and may be more useful for patients with a low left ventricular mass index at the initiation of haemodialysis.

Active vitamin D and vitamin D analogs stimulate fibroblast growth factor 23 production in osteocyte-like cells via the vitamin D receptor.

Osteocytes play an important role in the regulation of serum phosphorus by producing fibroblast growth factor 23 (FGF23). FGF23 production is stimulated by 1α,25-dihydroxyvitamin D in osteocytes. However, it is unclear whether vitamin D induces FGF23 production in osteocytes directly. Therefore, we investigated vitamin D-induced FGF23 production in osteocyte-like cells derived from MC3T3-E1 osteocyte progenitor cells. We also investigated differences in the induction of FGF23 by 1α,25-dihydroxyvitamin D and various vitamin D analogs. MC3T3-E1 cells were differentiated into osteocyte-like cells (MCT3-E1-OLCs) by treatment with various agents including ß-glycerophosphate and ascorbic acid. MCT3-E1-OLCs were stimulated with 1α,25-dihydroxyvitamin D3 and subsequent FGF23 gene expression was 2631 ± 605 times higher compared with untreated cells. The expression of FGF23 in MCT3-E1-OLCs transfected with a knockdown sequence against vitamin D receptor (VDR) was significantly decreased compared with that in cells transfected with the control vector. Therefore, the induction of FGF23 in osteocytes by vitamin D may be primarily mediated via VDR. The potential of 25(OH)vitamin D3, paricalcitol, and maxacalcitol to induce FGF23 production was almost the same as that of 1α,25-dihydroxyvitamin D3. However, falecalcitriol and eldecalcitol demonstrated a reduced potential to induce FGF23 compared with 1α,25-dihydroxyvitamin D3. Our results demonstrate that FGF23 induction is different among the analogs of 1α,25-dihydroxyvitamin D3. Therefore, an appropriate vitamin D analog should be chosen for each patient with mineral and bone disorder, considering its effect on FGF23 production.

An Analysis of Medication Adherence and Patient Preference in Long-term Stable Maintenance Hemodialysis Patients in Japan.

Objective This follow-up survey report describes medication adherence and patient preferences, beliefs, and expectations of maintenance hemodialysis treatment in Japan. Methods This patient-reported questionnaire-based survey was conducted in six regions in Japan from September 2016 to November 2016. Patients The questionnaire was provided to 700 patients (50-79 years old) on maintenance hemodialysis for >3 years who were members of the Japan Association of Kidney Disease Patients. Patients were randomly selected by a stratified sampling method based on patient distribution observed from the Japanese Society for Dialysis Therapy Renal Data Registry. Results A total of 524 (74.9%) complete patient questionnaires were evaluated; the mean (SD) age was 66.6 (7.2) years (men, 63.4%) with a dialysis vintage of 16.9 (9.1) years. Adherence was high for all types of medications: between 76.7% for phosphate binders and 95.7% for antidiabetic medications. The most common reason for a missed dose was forgetting to take medication [52.5% (117/223)]. Patient preference for oral medication was as low as 0.9% (1/110), 9% (31/345), and 2.9% (2/69) for patients who felt mental burden, felt no mental burden, and neither, respectively, with their current treatment regimen. In addition, 37.8% (198/524) of patients responded that the elimination of 1 medication (1 tablet) would reduce their mental burden. Conclusion The results of this survey show that overall medication adherence is high in Japanese patients on maintenance hemodialysis. While many patients perceive an absence of mental burden, they still prefer to avoid oral medication when possible.

Intravenous Maxacalcitol Therapy Correlates with Serum Fibroblast Growth Factor 23 Levels in Hemodialysis Patients Independent of Serum Phosphate or Calcium Levels.

Fibroblast growth factor 23 (FGF23) is a regulator of phosphate and vitamin D homeostasis that carries out primary bone- and mineral-related physiological functions to increase renal phosphate excretion and reduce 1α-hydroxylation of 25-hydroxyvitamin D. In a negative endocrine feedback loop, 1,25-dihydroxyvitamin D also stimulates FGF23 secretion. Previous studies have assessed the correlation between vitamin D receptor activator therapy and FGF23 concentrations, and to our knowledge, none has assessed the correlation between intravenous (i.v.) maxacalcitol therapy and FGF23 concentration in hemodialysis patients. Subjects included 148 patients on maintenance hemodialysis. Serum FGF23 concentrations were measured. The correlations among serum FGF23 concentrations with i.v. maxacalcitol therapy and other clinical parameters and medications were analyzed. Mean serum log FGF23 was 3.7 ± 0.8 pg/mL. After division into two equal groups based on median serum log FGF23 level, the percentages of patients administered i.v. maxacalcitol (60/74 [81.1%] vs. 45/74 [60.8%], p < 0.01) were significantly higher in the high log FGF23 group. The amounts of serum FGF23 concentrations had been significantly higher to the amounts of i.v. maxacalcitol per week dependency. Multivariate regression analysis showed that treatment with i.v. maxacalcitol was an independent predictor of serum FGF23 levels, regardless of phosphate or calcium concentrations. i.v. maxacalcitol correlates with serum FGF23 concentration in hemodialysis patients, independent of serum phosphate or calcium concentrations.

A Survey of Drug Burden in Patients Undergoing Maintenance Hemodialysis in Japan.

Objective This report presents a part of a survey pertaining to drug burden in maintenance hemodialysis patients in Japan. Methods A patient-reported questionnaire-based survey was conducted from September to November 2016 in six regions in Japan. Patients A total of 700 patients (50-79 years old) on maintenance hemodialysis for >3 years and members of the Japan Association of Kidney Disease Patients (JAKDP) were provided with the questionnaire. They were randomly selected using stratified sampling according to patient distribution observed from the Japanese Society for Dialysis Therapy Renal Data Registry (JSDT JRDR). Results A total of 524 (74.9%) patient questionnaires were evaluated [mean (standard deviation; SD) age, 66.6 (7.2) years; males, 63.4%; dialysis vintage, 16.9 (9.1) years]. Patients' age, gender, and regional distribution were similar to the JSDT JRDR. They were taking an average (SD) of 16.4 (8.34) and 16.3 (8.55) oral medications/day on dialysis and nondialysis days, respectively. A majority of the patients were taking ≥10 oral medications/day on dialysis (75.1%) and nondialysis (74.4%) days, with phosphate binders being the most taken (7.0 tablets/day). A similar proportion (74.4%, 72.9%, respectively) was taking ≥6 different types of oral medications/day. Most patients were taking oral medications 3 (31%, 33%), 4 (24%, 22%), and ≥5 times (31%, 30%) a day, respectively. The drug burden was similar on dialysis and nondialysis days and did not vary with dialysis vintage. Conclusion The number, type, and frequency of oral medications in maintenance hemodialysis patients are high in Japan. The proportion of phosphate binders was highest among the prescription medications.

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression.

BACKGROUND: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). METHODS: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. RESULTS: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. CONCLUSION: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.

Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies.

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short- and long-term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end-stage renal disease requiring dialysis or transplantation is attracting increased attention.

FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells.

BACKGROUND: FGF23 plays an important role in calcium-phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium-phosphorus metabolism. METHODS: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. RESULTS: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. CONCLUSION: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells.

Severe refractory infection due to renocolic fistula in a patient with a giant kidney and ADPKD undergoing long-term hemodialysis.

Renocolic fistula is rare. Renal cyst infection is a serious complication in patients with autosomal dominant polycystic kidney disease (ADPKD). We present a case of refractory renal cyst infection due to renocolic fistula in a patient with ADPKD. A 65-year-old man with ADPKD on hemodialysis visited our hospital with complaints of fever and left abdominal pain. We diagnosed renal cyst infection with abdominal computed tomography scans. After hospitalization, gas shadow was observed in the left renal cyst. Percutaneous puncture of the cyst was performed. Because contrast medium into the left renal cyst through nephrostomy was flowing into the descending colon, renocolic fistula was diagnosed. The patient underwent nephrectomy combined with partial descending colonic resection and splenectomy, but he died. Renocolic fistula is probably hidden in some refractory renal cyst infection cases. This case report aims to create awareness of renocolic fistula, so that early diagnosis and intervention can salvage such patients.

Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model.

Previous clinical and experimental studies have indicated that magnesium may prevent vascular calcification (VC), but mechanistic characterization has not been reported. This study investigated the influence of increasing magnesium concentrations on VC in a rat aortic tissue culture model. Aortic segments from male Sprague-Dawley rats were incubated in serum-supplemented high-phosphate medium for 10 days. The magnesium concentration in this medium was increased to demonstrate its role in preventing VC, which was assessed by imaging and spectroscopy. The mineral composition of the calcification was analyzed using Fourier transform infrared (FTIR) spectroscopic imaging, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) mapping. Magnesium supplementation of high-phosphate medium dose-dependently suppressed VC (quantified as aortic calcium content), and almost ablated it at 2.4 mm magnesium. The FTIR images and SEM-EDX maps indicated that the distribution of phosphate (as hydroxyapatite), phosphorus and Mg corresponded with calcium content in the aortic ring and VC. The inhibitory effect of magnesium supplementation on VC was partially reduced by 2-aminoethoxy-diphenylborate, an inhibitor of TRPM7. Furthermore, phosphate transporter-1 (Pit-1) protein expression was increased in tissues cultured in HP medium and was gradually-and dose dependently-decreased by magnesium. We conclude that a mechanism involving TRPM7 and Pit-1 underpins the magnesium-mediated reversal of high-phosphate-associated VC.

Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor.

AIM: Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD-mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD-mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. METHODS: Aortic segments from 7-week-old male Sprague-Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. RESULTS: Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p＜0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. CONCLUSION: These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor.

Expression and localization of fibroblast growth factor (FGF)23 and Klotho in the spleen: its physiological and functional implications.

The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220+ CD21/CD35+ CD1d+ CD43- marginal zone B cells. These cells also expressed FGF receptor 1, indicating that Klotho-positive B cells could respond to FGF23. Plasmacytoid dendritic cells (pDCs) with CD11c+ CD45R/B220+ CD11b- CD8α- were found to produce FGF23. Klotho-positive cells and FGF23-producing cells were present in close proximity to each other, suggesting that FGF23 produced by pDCs may act within a limited area. These findings indicate that FGF23-Klotho signaling could play a biological or immunological role in the spleen.

Effects of Cyclophosphamide Pulse Therapy on the Clinical and Histopathological Findings, Particularly Crescent Formation, in a Patient with Adult-onset Steroid-refractory Henoch-Schönlein Purpura Nephritis.

A 29-year-old woman was diagnosed with Henoch-Schönlein purpura nephritis (HSPN) based on the presence of purpura and histopathological findings showing crescent formation, mesangial proliferation and IgA deposition in the glomerular mesangium. She was treated with high-dose steroids; however, the nephritic syndrome persisted. Therefore, we diagnosed her with steroid-resistant HSPN and decided to add treatment with cyclosphamide pulse therapy. After one year of treatment, the histopathological findings, including crescent formation and IgA deposition, improved, as confirmed on a renal biopsy, and the patient fulfilled the criteria for complete remission. Cyclophosphamide pulse therapy may be considered an effective treatment for intractable HSPN.

Mineral Composition of Phosphate-Induced Calcification in a Rat Aortic Tissue Culture Model.

AIM: High phosphorus conditions promote vascular calcification (VC) in both chronic kidney disease (CKD) patients and experimental models. However, the composition of medial calcification has not been accurately determined, so the objective of this study was to evaluate the mineral composition of calcification in a tissue culture model, not a cell culture system. METHODS: Aortic rings obtained from male Sprague-Dawley rats were incubated in serum-supplemented medium for 10 days. The inorganic phosphate (Pi) concentration of the medium was increased to induce VC, which was assessed by histology, imaging, and spectroscopy. The mineral composition of the calcification was analyzed using Fourier transform infrared (FTIR) spectroscopic imaging, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) mapping. RESULTS: The calcium content significantly increased only in aortic rings cultured for 10 days in the high-Pi medium (HiP: 3.8 mmol/L). The concentration of the phosphate transporter Pit-1 in the aortic tissue exposed to HiP was higher than that in the control incubated sections. The FTIR images and spectra indicated that PO4(3-) was mostly distributed as hydroxyapatite in the medial calcification of aortic rings cultured in HiP. A small quantity of carbonate was identified. The SEM-EDX overlay map demonstrated that phosphorus and calcium simultaneously accumulated and localized in the area of medial calcification induced by exposure to HiP. CONCLUSION: This is the first report of accurate determination of the chemical composition of aortic medial calcification. Exposure to high Pi concentration augments aortic calcification via an increase in Pit-1, which mainly contains calcium phosphate.

Safety and efficacy evaluation of lanthanum carbonate for hyperphosphatemia in end-stage renal disease patients.

In end-stage renal disease patients, various abnormalities of bone mineral metabolism adversely affect mortality. Hyperphosphatemia is known to adversely affect mortality and quality of life in chronic kidney disease patients and has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. Thus, hyperphosphatemia is the main treatment target indicated in several guidelines for chronic kidney disease-mineral and bone disorder treatment. Phosphate binders are typically required for the management of hyperphosphatemia because dietary phosphorus restriction and phosphorus removal by hemodialysis alone are insufficient. We are able to prescribe five phosphate binders (calcium carbonate, sevelamer HCl, lanthanum carbonate (LaC), bixalomer, and ferric citrate) to Japanese hemodialysis patients. LaC is the most powerful noncalcium-containing phosphate binder for the treatment of hyperphosphatemia. In this chapter, we discuss the efficacy and safety of LaC, the safety of which has been under debate. In particular, we consider its toxic effects on the skeletal system. LaC is effective for hyperphosphatemia treatment in end-stage renal failure patients. It has been shown to be able to decrease serum fibroblast growth factor-23 levels. This result suggests that it may have beneficial effects on the cardiovascular system in patients undergoing renal replacement therapy. However, the effects of LaC remain obscure. Further investigations are required. No negative effects of LaC on bone metabolism or bone morphometry have been reported, but long-term clinical data are needed.

Tonsillectomy with steroid pulse therapy has more effect on the relapse rate than steroid pulse monotherapy in IgA nephropathy patients.

AIMS: Both steroid pulse (SP) monotherapy and the combination of tonsillectomy and SP therapy (TSP) are effective for achieving clinical remission (CR), defined as negative hematuria and proteinuria, in patients with IgA nephropathy (IgAN). The role of tonsillectomy in the treatment of IgAN has been analyzed only from the aspect of CR or renal survival after TSP treatment, so there is no evidence of its effect on the relapse after CR. METHODS: We retrospectively investigated relapse (re-appearance of urinary abnormalities) from CR after TSP or SP monotherapy in 62 IgAN patients (mean follow-up, 70.1 ± 35.3 months). The SP therapy comprised 0.5 g methylprednisolone administered intravenously on 3 consecutive days followed by oral prednisolone (30 mg/day) on 4 consecutive days, with the course repeated 3 times. Oral prednisolone (30 mg/day) was then given on alternative days and gradually tapered and finished over 1 year. Tonsillectomy was performed either before or within 6 months of starting SP therapy. RESULTS: At baseline, the mean age was 34.6 years, the mean serum creatinine (Cr) level was 0.9 mg/dl, and the mean level of proteinuria was 876 mg/day. There were no differences between the TSP group (41 patients) and SP monotherapy group (21 patients). In total, 24 of the TSP and 10 of the SP patients achieved CR. Of the 34 patients who achieved CR, 13 relapsed after TSP or SP monotherapy. Using Kaplan-Meier analysis, tonsillectomy was associated with a lower incidence of relapse from CR after treatment (p = 0.045). Multivariate Cox regression analysis revealed that tonsillectomy reduced the rate of from CR after SP therapy. CONCLUSION: Tonsillectomy was associated with a reduction in the relapse rate from CR after SP therapy in IgAN patients.