Long-term benefits of switching from oral to intravenous calcimimetics in patients on hemodialysis.

AIM: In this study, we aimed to investigate the long-term benefits of switching from oral to intravenous calcimimetics in patients on hemodialysis. MATERIALS AND METHODS: Patients on maintenance hemodialysis at our institution who switched from oral to intravenous calcimimetics between March 1, 2017 and October 31, 2018 were enrolled. We compared tablet number; chronic kidney disease-mineral and bone disorder (CKD-MBD)-related drug cost; and serum corrected calcium, serum phosphorous, and serum intact parathyroid hormone levels before and 1, 2, and 3 years after switching from oral to intravenous calcimimetics. RESULTS: There were 15 patients (11 males and 4 females; mean age 60.9 ± 9.2 years). The tablet numbers and CKD-MBD-related drug cost before and 3 years after switching to calcimimetics were 12.1 ± 8.1 tablets/day vs. 8.4 ± 5.0 tablets/day (p = 0.0371) and 9,654.5 ± 6,206.8 yen (87.8 ± 56.4 U.S. dollars)/week vs. 7,231.7 ± 3,490.9 yen (65.7 ± 31.7 U.S. dollars)/week (p = 0.0406), respectively. CONCLUSION: Switching from oral to intravenous calcimimetics decreased intact parathyroid hormone levels and reduced the tablet numbers and CKD-MBD-related drug cost for a long period without significant adverse effects.

Occurrence of fever in cell-free and concentrated ascites reinfusion therapy is not related to the primary disease or nature of ascites.

Cell-free and concentrated ascites reinfusion therapy (CART) is a treatment for refractory ascites wherein filtered and concentrated ascitic fluid is reinfused. Although fever is one of the side effects of CART, its cause is not clear. Patients who underwent at least one CART session between June 2011 and May 2021 at our medical center were retrospectively enrolled in the study. They were classified according to the primary disease and nature of ascites. Ninety patients were included in this study. Increase in body temperature (BT) after CART was observed, regardless of the primary disease and nature of ascites. The difference in temperature before and after CART did not differ based on the primary disease [cancerous (including hepatocellular carcinoma, ovarian cancer) and non-cancerous] and nature of ascites. Elevated BT and fever after CART are not related to the primary disease and nature of the ascites.

[Investigation of the safety and usefulness of a renal biopsy for older elderly patients ≥75 years old].

AIM: We herein report the safety and usefulness of a kidney biopsy in older elderly patients (≥75 years old). METHODS: A retrospective observational study was conducted in older elderly patients who had received a renal biopsy at the Department of Nephrology, Shimane University Hospital, from January 1, 2008, to December 31, 2018. The native renal biopsy results of 52 later-stage elderly patients were analyzed (29 men and 23 women). RESULTS: The most common indication for a renal biopsy was nephrotic syndrome (n = 22), followed by rapidly progressive glomerulonephritis (n = 12) and asymptomatic urinary abnormalities (n = 12). The most common pathological diagnosis was membranous nephropathy (n = 12), followed by ANCA-associated nephritis (n= 8), minimal change nephrotic syndrome (6 case), membranoproliferative glomerulonephritis (n = 5), IgA nephropathy (n = 4), and diabetic nephropathy (n = 3). The concordance rate between the clinical and pathological diagnoses was 53.8%. The only complication of the renal biopsy was hemorrhaging requiring blood transfusion (1 patient; 1.9%). The hemoglobin level decreased by 0.5±0.05 d/dL after the biopsy. CONCLUSION: The rate of serious complications associated with a renal biopsy was comparable to that in previous reports in younger patient. Renal biopsies can therefore be safely performed even in older elderly patients. The concordance rate of the clinical and pathological diagnoses was about 50%. Therefore, renal biopsies should be performed in older elderly patients when necessary.

Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration.

To address the lack of organs for transplantation, we previously developed a method for organ regeneration in which nephron progenitor cell (NPC) replacement is performed via the diphtheria toxin receptor (DTR) system. In transgenic mice with NPC-specific expression of DTR, NPCs were eliminated by DT and replaced with NPCs lacking the DTR with the ability to differentiate into nephrons. However, this method has only been verified in vitro. For applications to natural models, such as animal fetuses, it is necessary to determine the optimal administration route and dose of DT. In this study, two DT administration routes (intra-peritoneal and intra-amniotic injection) were evaluated in fetal mice. The fetus was delivered by caesarean section at E18.5, and the fetal mouse kidney and RNA expression were evaluated. Additionally, the effect of the DT dose (25, 5, 0.5, and 0.05 ng/fetus-body) was studied. Intra-amniotic injection of DT led to a reduction in kidney volume, loss of glomeruli, and decreased differentiation marker expression. The intra-peritoneal route was not sufficient for NPC elimination. By establishing that intra-amniotic injection is the optimal administration route for DT, these results will facilitate studies of kidney regeneration in vivo. In addition, this method might be useful for analysis of kidney development at various time points by deleting NPCs during development.

[A case of right femoral artery thromboembolism in steroid-dependent nephrotic syndrome].

A 37-year-old man diagnosed with minimal change nephrotic syndrome at the age of 17, was admitted to hospital with leg pain. He had relapsed nephrotic syndrome and thromboembolism of the right femoral and middle cerebral arteries. He was treated with steroid pulse therapy and thrombectomy. Right lower extremity necrosis developed and a below-knee amputation was performed. His nephrotic syndrome and the amputated lower extremity necrosis subsequently improved. Arterial thrombosis is a rare complication of nephrotic syndrome; however, it is a severe complication. Prophylactic anticoagulation should be considered in patients with an increased risk of thrombosis.

Low glomerular number at birth can lead to the development of chronic kidney disease.

Chronic kidney disease (CKD) prevalence is increasing worldwide, and reducing the number of patients with CKD is of utmost importance. The environment during the fetal, perinatal, and early childhood stages may influence CKD development (developmental origins of health and disease). Under conditions of maternal malnutrition, the glomerular number of infants reduces, and the risk of developing CKD may increase. Nephron progenitor cells and ureteric buds interact with each other to form glomeruli at the tip of the ureteric bud. Thus, the number of glomeruli is determined by the number of ureteric bud branches, which are reportedly decreased due to maternal malnutrition, in turn reducing the glomerular number. Four possible mechanisms can explain the low glomerular number resulting from maternal malnutrition: 1) suppression of c-Ret expression, 2) suppression of nephron formation by renin-angiotensin-aldosterone system inhibition, 3) exposure to excess glucocorticoids, and 4) promotion of apoptosis. Additionally, nephron formation does not continue after birth in humans. Therefore, a low glomerular number at birth is a lifelong burden on the glomeruli and increases the risk of developing CKD. Therefore, it is important to maintain the glomerular number at birth. Accurate glomerular counts are essential for conducting studies on the glomerular number. The dissector/fractionator method is the gold standard; however, it can only be performed at some institutions. Recently, methods have been developed to measure the glomerular number by combining computed tomography and pathological examination and measure the glomerular count using magnetic resonance imaging. Models of decreased and increased glomerular numbers have been developed. Moreover, research regarding the causes of decreased glomerular number and its relationship with development of lifestyle-related diseases and renal dysfunction has significantly progressed, furthering our understanding of the importance of glomerular number.

Cystatin C as a Potential Blood Biomarker for Sarcoidosis: A Case Report.

Sarcoidosis is a multi-organ medical condition that is characterized by the formation of granulomas. We aimed to identify a correlation between each sarcoidosis blood biomarker and cystatin C (Cys-C) in sarcoidosis patients. We report a case of a 60-year-old man with sarcoidosis. The correlation between his Cys-C and each blood biomarker level and that between each blood biomarker and serum creatinine levels were determined using linear regression. Serum Cys-C correlated with each blood biomarker of sarcoidosis, while creatinine did not. These findings suggest that Cys-C is a potential blood biomarker for sarcoidosis.

Indications for Percutaneous Drainage in Patients with Huang Class 3B Emphysematous Pyelonephritis: A Case Report and Literature Review.

Emphysematous pyelonephritis (EPN) is a severe urinary tract infection common in patients with diabetes. Nephrectomy is recommended when the Huang classification is ≥3B. We herein report a case in which nephrectomy was avoided using antimicrobial agents and percutaneous drainage (PCD). A 59-year-old man was diagnosed with EPN (Huang classification 3B). The causative bacteria were Escherichia coli. Despite high-risk factors, EPN was cured with kidney preservation and PCD because the emphysema and abscess were not extensive. Thus, PCD should be considered in patients with Huang Class 3B EPN and high-risk factors if emphysema and abscess are not extensive.

Utility of renal biopsy in differentiating idiopathic multicentric Castleman disease from IgG4-related disease.

Idiopathic multicentric Castleman disease (iMCD) is a subtype of human herpesvirus type 8 (HHV-8)-related Castleman disease that causes multi-organ damage, including kidney damage due to polyclonal lymphoproliferation and interleukin (IL)-6-induced cytokine storm. However, its renal pathological findings are unclear. We report the case of a woman in her 80 s who was diagnosed with iMCD based on renal pathological findings. Five years ago, hypergammaglobulinemia was detected, and her renal function declined. Renal biopsy revealed plasma cells infiltrating the stroma. Immunostaining revealed numerous IgG4-positive plasma cells. The serum IgG4 level was high, and she was initially diagnosed with IgG4-related disease (IgG4-RD) and treated with steroids. However, the therapeutic effect was poor. On re-examination, computed tomography revealed lymphadenopathy around the aorta and spleen. Renal histopathology showed numerous IL-6-positive plasma cells. Anemia and C-reactive protein (CRP) positivity persisted despite steroid administration. HHV-8 was negative, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome was not suspected. Thus, iMCD was diagnosed. Based on previous reports, there is no significant difference in IgG4 levels between iMCD and IgG4-RD, and IgG4-positive plasma cell infiltrates were observed in iMCD-affected organs. Therefore, it may be difficult to distinguish iMCD from IgG4-RD. In this case, high-serum IL-6 and CRP were observed, which are usually not seen in IgG4-RD but are common findings in iMCD, leading to the diagnosis. Patients with deep lymphadenopathy may be diagnosed with iMCD based on renal pathological findings. Renal biopsy is recommended for patients with suspected iMCD and decreased renal function.

A 3-Mbp fragment on rat chromosome 1 affects susceptibility both to stroke and kidney injury under salt loading in the stroke-prone spontaneously hypertensive rat: a genetic approach using multiple congenic strains.

We have previously reported that a major quantitative trait locus (QTL) responsible for susceptibility to salt-induced stroke in the stroke-prone spontaneously hypertensive rat (SHRSP) is located in a 3-Mbp region on chromosome 1 covered by SHRSP.SHR-(D1Rat23-D1Rat213)/Izm (termed Pr1.31), a congenic strain with segments from SHRSP/Izm introduced into the stroke-resistant SHR/Izm. Here, we attempted to narrow down the candidate region on chromosome 1 further through analyses of subcongenic strains constructed for the target region. Simultaneously, salt-induced kidney injury was evaluated through the measurement of urinary albumin and the gene expression of renal tubular injury markers (Kim-1 and Clu) to explore a possible mechanism leading to the onset of stroke. All subcongenic strains examined in this study showed lower susceptibility to salt-induced stroke than SHRSP. Interestingly, Pr1.31 had the lowest stroke susceptibility when compared with newly constructed subcongenic strains harboring fragments of the congenic sequence in Pr1.31. Although Kim-1 and Clu expression after 1 week of salt loading in Pr1.31 did not differ significantly from those in SHRSP, the urinary albumin level of Pr1.31 was significantly lower than those of the other subcongenic strains and that of SHRSP. The present results indicated that, although the congenic fragment in Pr1.31 harbored the gene(s) related to salt-induced organ damages, further genetic dissection of the candidate region was difficult due to multiple QTLs suggested in this region. Further analysis using Pr1.31 will unveil genetic and pathophysiological mechanisms underlying salt-induced end organ damages in SHRSP.

Administration of retinoic acid to pregnant mice increases the number of fetal mouse glomeruli.

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and CKD is a serious global health problem. Low glomerular number is one of the risk factors for CKD; therefore, the glomerular number is associated with the risk of CKD. Increasing the glomerular number above normal levels may reduce the risk of CKD. It has been reported that, in vitro, the addition of retinoic acid (RA) to the culture medium increases the glomerular number. However, there is no report of an increase in glomerular number above normal levels with the addition of RA in vivo. In this study, RA (20 mg/kg) was administered intraperitoneally to pregnant mice once at embryonic day (E) 10.5, E12.5, E14.5, or E16.5. The fetuses were harvested at E18.5 and fetal mouse kidneys were evaluated. Fetal kidney volume and weight were significantly increased in the E16.5 group compared to the control group. The total glomerular number in the E16.5 group was also approximately 1.46 times higher than that in the control group. In summary, we established a method to increase the glomerular number in the fetal kidney by administration of RA to pregnant mice at E16.5. These results will facilitate the investigation of whether CKD risk is reduced when the glomerular number increases above normal.

IgA Nephropathy that Developed as an Immune-related Adverse Event of Pembrolizumab Complicated with Interstitial Nephritis.

A 70-year-old man received pembrolizumab as a second-line treatment for squamous cell lung cancer of the lower right lobe. After three courses, proteinuria and hematuria were observed, which worsened after seven courses. He was diagnosed with a combination of IgA nephropathy and active interstitial nephritis. Steroid pulse therapy was started, and the dose of prednisolone was gradually reduced from 60 mg/day. Renal dysfunction as an immune-related adverse event of pembrolizumab monotherapy for non-small cell lung cancer has been reported previously. Therefore, establishing a system for the early detection and treatment that distinguishes immune-related glomerular diseases is essential.

Tetany Exacerbating Heart Failure: A Case Report.

Tetany is characterized by numbness and stiffness in the hands and feet caused by hypocalcemia, hypomagnesemia, and hyperventilatory alkalosis, primarily at peripheral neuromuscular junctions. Although hypocalcemia is common in critically ill patients, its diagnosis of hypocalcemia is complicated and sometimes overlooked. We encountered an 82-year-old woman with tetany that exacerbated heart failure. Pain and respiratory failure due to tetany are conditions that can lead to exacerbation of heart failure. Chronic renal failure is frequently associated with chronic heart failure, and regular follow-up of calcium, phosphorus, and magnesium levels is necessary for such patients.

Detection of Autosomal Dominant Polycystic Kidney Disease by Medical Checkup at an Early Stage.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. Although abdominal echography during medical checkup may be effective for the early detection of ADPKD, there are no reports of the early detection of ADPKD during medical checkup. We investigated whether there was a difference in renal function and total kidney volume (TKV) at the time of diagnosis due to differences in diagnostic triggers for ADPKD. METHODS: A total of 34 patients diagnosed with ADPKD between January 1, 2010, and December 31, 2020, at the Department of Nephrology, Shimane University Hospital, were included. The triggers for diagnosis of the renal cyst(s) were usually unintentional findings. These included findings observed upon routine medical checkups, computed tomography, or abdominal echography during examination for other diseases (incidental detection group) and cases referred to our department for renal dysfunction (renal dysfunction group), and "other" group. We compared the renal dysfunction group and the incidental detection group. RESULTS: The estimated glomerular filtration rate (eGFR) at diagnosis was significantly higher in the incidental detection group. The TKV was significantly lower in the incidental detection group than in the other group. The number of patients with eGFR > 45 mL/min/1.73 m2, for which tolvaptan was safe and effective, was significantly higher in the incidental detection group than in the renal dysfunction group. CONCLUSION: Our study shows that medical checkup enables early detection of ADPKD. This is important because ADPKD may have serious complications. The present study did not examine the age at which abdominal echography screening for the early detection of ADPKD was more useful or cost-effective; thus, further research is needed to ascertain this.

Effectiveness of CKD Exacerbation Countermeasures in Izumo City.

To diagnose chronic kidney disease (CKD) at an early stage, it is important to promote appropriate health guidance and consultation recommendations through regular medical examinations and implementation of continuous high-quality and appropriate treatment. From fiscal year (FY) 2018, Izumo City has initiated the "Izumo City CKD Exacerbation Countermeasures" program. In this study, we aimed to report on the methods undertaken and the effects of this program. Residents aged 40-74 years who underwent specific health checkups from the Izumo City National Health Insurance in FY2018 and FY2019 were included. The rates of CKD re-examination candidates, re-examinations implementation, nephrologist referrals, and health guidance referrals between FY2018 and FY2019 were compared. The rate of CKD re-examination candidates in both years remained unchanged at approximately 7%. The rate of re-examination implementation in FY2019 significantly increased relative to that in FY2018 (p < 0.001). Subsequent re-examination candidate trends showed that the rate of nephrologist referrals did not increase. However, the rate of city health guidance referrals significantly increased (p < 0.001). Increase in the re-examination and health guidance examination rates indicate improved awareness of CKD among the public and family doctors, and it is expected to prevent CKD exacerbation in the future.

A Remarkable Elevation in the Procalcitonin Levels Due to Diabetic Ketoacidosis in a Hemodialysis Patient.

Procalcitonin (PCT), a marker of the inflammatory response during infections, can be elevated by diabetic ketoacidosis (DKA). A male patient in his 50s with diabetic nephropathy on hemodialysis presented with vomiting and a reduced level of consciousness and was diagnosed with DKA. His PCT level was markedly elevated, but bacterial cultures (blood, urine, and stool) were negative. The PCT level decreased after DKA improvement. In this patient, DKA probably enhanced the PCT levels. As DKA can increase the PCT levels, an elevation of the PCT levels in DKA patients may not be indicative of infectious diseases, and non-infectious causes of DKA should therefore be considered.

In vivo regeneration of interspecies chimeric kidneys using a nephron progenitor cell replacement system.

Kidney regeneration is expected to be a new alternative treatment to the currently limited treatments for chronic kidney disease. By transplanting exogeneous nephron progenitor cells (NPCs) into the metanephric mesenchyme of a xenogeneic foetus, we aimed to regenerate neo-kidneys that originate from transplanted NPCs. Previously, we generated a transgenic mouse model enabling drug-induced ablation of NPCs (the Six2-iDTR mouse). We demonstrated that eliminating existing native host NPCs allowed their 100% replacement with donor mouse or rat NPCs, which could generate neo-nephrons on a culture dish. To apply this method to humans in the future, we examined the possibility of the in vivo regeneration of nephrons between different species via NPC replacement. We injected NPCs-containing rat renal progenitor cells and diphtheria toxin below the renal capsule of E13.5 metanephroi (MNs) of Six2-iDTR mice; the injected MNs were then transplanted into recipient rats treated with immunosuppressants. Consequently, we successfully regenerated rat/mouse chimeric kidneys in recipient rats receiving the optimal immunosuppressive therapy. We revealed a functional connection between the neo-glomeruli and host vessels and proper neo-glomeruli filtration. In conclusion, we successfully regenerated interspecies kidneys in vivo that acquired a vascular system. This novel strategy may represent an effective method for human kidney regeneration.

A case of acute kidney injury and disseminated intravascular coagulation associated with influenza B viral infection.

There are few reports of acute kidney injury (AKI) associated with influenza viral infection. We treated a case of AKI that developed after an influenza B viral infection. A 35-year-old man visited a local physician for a fever and was diagnosed with influenza B. He was prescribed laninamivir, then returned to the physician 5 days later with dyspnea and was referred to Hospital A. Upon admission, respiratory arrest developed, for which he received tracheal intubation and mechanical ventilation. AKI was noted after admission and the patient was transferred to our hospital the next day. AKI and disseminated intravascular coagulation (DIC) were present at the time of transfer, thus a transfusion and continuous hemodiafiltration (CHDF) were performed, and administrations of thrombomodulin alpha and antithrombin III were initiated. Although the patient had DIC, AKI, and disturbance of consciousness, and was in a clinical state resembling influenza-associated encephalopathy, there was no clear abnormality shown in CT scans of the head. Urine output, renal function, and respiratory condition gradually improved, thus CHDF was stopped and extubation performed. The patient had no complications and was discharged on hospital day 22. Some reports have been presented regarding cases of AKI due to rhabdomyolysis associated with influenza viral infection, whereas our patient developed AKI as a complication of an influenza B viral infection without rhabdomyolysis or hemolytic uremic syndrome. Influenza B may cause AKI and DIC, and affected patients can be in a serious condition requiring immediate attention.