Corrigendum to "Detecting MUC1 Variants in Patients Clinicopathologically Diagnosed With Having Autosomal Dominant Tubulointerstitial Kidney Disease"Kidney International Reports, Volume 7, Issue 4, April 2022, Pages 857-866.

[This corrects the article DOI: 10.1016/j.ekir.2021.12.037.].

Detecting MUC1 Variants in Patients Clinicopathologically Diagnosed With Having Autosomal Dominant Tubulointerstitial Kidney Disease.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD)-MUC1 is predominantly caused by frameshift mutations owing to a single-base insertion into the variable number tandem repeat (VNTR) region in MUC1. Because of the complexity of the variant hotspot, identification using short-read sequencers (SRSs) is challenging. Although recent studies have revealed the usefulness of long-read sequencers (LRSs), the prevalence of MUC1 variants in patients with clinically suspected ADTKD remains unknown. We aimed to clarify this prevalence and the genetic characteristics and clinical manifestations of ADTKD-MUC1 in a Japanese population using an SRS and an LRS. Methods: From January 2015 to December 2019, genetic analysis was performed using an SRS in 48 patients with clinically suspected ADTKD. Additional analyses were conducted using an LRS in patients with negative SRS results. Results: Short-read sequencing results revealed MUC1 variants in 1 patient harboring a cytosine insertion in the second repeat unit of the VNTR region; however, deeper VNTR regions could not be read by the SRS. Therefore, we conducted long-read sequencing analysis of 39 cases and detected MUC1 VNTR variants in 8 patients (in total, 9 patients from unrelated families). With the inclusion of family-affected patients (n = 31), the median age at the development of end-stage kidney disease (ESKD) was 45 years (95% CI: 40-40 years). Conclusion: In Japan, the detection rate of MUC1 variants in patients with clinically suspected ADTKD was 18.8%. More than 20% of patients with negative SRS results had MUC1 variants detected by an LRS.

Infected hepatic and renal cysts: differential impact on outcome in autosomal dominant polycystic kidney disease.

BACKGROUND: Infected cysts are a frequent and serious complication of autosomal dominant polycystic kidney disease. Such infections are classified into those affecting hepatic cysts and those affecting renal cysts. The purpose of this study was to compare the clinical course of infected hepatic cysts with that of infected renal cysts in patients with autosomal dominant polycystic kidney disease. METHODS: We analyzed 43 patients referred to us for additional treatment of severely infected cysts between January 2004 and December 2006. All patients who required further treatment in addition to antibiotic therapy were included. RESULTS: Aspiration was performed in all 28 patients with infected hepatic cysts. As a result, 17 patients were cured, 4 remain under treatment, and 6 died. One patient was cured by partial hepatectomy. Among the 15 patients with renal cysts, aspiration was performed in 4 with identifiable infected cysts, while renal transcatheter arterial embolization after appropriate antibiotic therapy was performed in 11 without identifiable infected cysts. No patient developed recurrence. CONCLUSION: In patients with infected renal cysts, aspiration or renal transcatheter arterial embolization after appropriate antibiotic therapy was effective. Although aspiration was often effective in patients with infected hepatic cysts, a good outcome was less likely than in those with renal cysts.

A case of primary hyperparathyroidism with severe bone and renal changes.

We report a 79-year-old Japanese woman who had primary hyperparathyroidism (HPT) with end-stage renal disease and severe bone changes. In 2004, she began to experience pain in her shoulders and knees, as well as muscle weakness and anorexia. She already had renal failure with a serum Cr of 4.7 mg/dl, while serum calcium was 9.6 mg/dl, PTH was 2,710 pg/ml, and serum alkaline phosphatase was 923 mU/ml. Multiple fractures of the pelvic bones and lumbar spine, osteoporosis, and subperiosteal bone resorption were detected. Although hemodialysis (HD) was started in February 2005, her symptoms became more severe. Total parathyroidectomy (PTX) and right iliac crest bone biopsy were performed. Histomorphometric analysis of the cancellous bone indicated a diagnosis of osteitis fibrosa, but a reduction of cortical bone and near absence of cancellous bone were also apparent. This showed that bone resorption by osteoclasts was predominant over bone formation by osteoblasts. Soon after PTX, her pain subsided completely. We conclude that primary HPT should be detected and treated early enough to avoid renal damage, since renal dysfunction markedly accelerates bone changes in patients with primary HPT.

Plasma adiponectin: a predictor of coronary heart disease in hemodialysis patients--a Japanese prospective eight-year study.

BACKGROUND/AIM: Plasma adiponectin may play a protective role in the pathogenesis of cardiovascular disease in hemodialysis (HD) patients. We examined the effect of plasma adiponectin levels on the prognosis of the HD patients. METHODS: 68 HD patients (male:female = 38:30) were subjected to plasma adiponectin measurement in 1998 and followed up over 8 years. RESULTS: Plasma adiponectin concentrations differed between male and female patients (9.3 vs. 15.7 microg/ml). The plasma adiponectin concentration as a whole was positively correlated with serum high-density lipoprotein cholesterol and negatively with serum creatinine and waist circumference. During an 8-year follow-up, the cardiac events occurred in 7 of 38 men and in 10 of 30 women. Cox's proportional hazard model analysis in a stepwise manner revealed that coronary heart disease (CHD) was associated with intact parathyroid hormone concentration, age, and the presence of diabetes in men whereas plasma adiponectin concentration was the most powerful single predictor in women. The impact of the plasma adiponectin concentration was strengthened by Kaplan-Meier survival analysis. In the group with a lower plasma adiponectin concentration, CHD events were significantly increased in men (p = 0.043) and in women (p = 0.007). CONCLUSION: Plasma adiponectin concentration may predict CHD outcomes in HD patients.

Changes in the activities of daily living (ADL) in relation to the level of amputation of patients undergoing lower extremity amputation for arteriosclerosis obliterans (ASO).

BACKGROUND: The relationship between the level of amputation and the activities of daily living (ADL) in Japanese patients with arteriosclerosis obliterans (ASO) is unclear. METHODS AND RESULTS: In the present study 81 patients with ASO who underwent lower extremity amputation and were discharged from hospital after rehabilitation we evaluated. The patients were classified into 4 groups: toe amputation group (Toe), heel-preserving amputation group (Heel), below-knee amputation group (BK), and above-knee amputation group (AK). ADL at discharge and factors affecting the length of hospitalization were determined. Patients were walking at discharge in 94.5%, 94.0%, 59.0%, and 0.0% of the Toe, the Heel, BK, and AK group, respectively. However, the ratio of patients able to walk independently was 68% in the Toe group and 19% in the Heel group. In addition, the length of hospital stay was significant shorter in the Toe group than in the other groups. Factors affecting the length of hospital stay were the amputation level, cerebrovascular disease, reoperation, and diabetes. CONCLUSIONS: ADL are less affected and the length of hospital stay is shorter for patients undergoing toe amputation than other levels of lower extremity amputation. However, heel-preserving amputation maintains a comparable level of ADL in terms of ambulatory discharge.

[Modified FOLFOX6 in a patient on hemodialysis with metastatic colorectal cancer].

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, chemotherapy for a hemodialysis patient should be considered with due care. We administered chemotherapy of modified FOLFOX6 to a patient on hemodialysis with inoperable metastatic colorectal cancer, and measured his plasma concentration of total platinum and non-protein-bound platinum. Since there is no reported case of oxaliplatin use in patients on hemodialysis so far, we evaluated whether it could be safely used for such patients. We made a dose escalation study with 40, 50, 60, 70 and 85 mg of oxaliplatin, and evaluated the pharmacokinetics at each dose. AUC was 5.67-10.21 mg/L x h. The dialysis removal rate was 84.0%. Although this patient could accept it relatively safely without any severe side effect, the optimal dosage and the timing of hemodialysis for inoperable metastatic colorectal cancer patients should be determined by a further study using more cases.

Induction of anti-carbonic-anhydrase-II antibody causes renal tubular acidosis in a mouse model of Sjogren's syndrome.

BACKGROUND/AIM: We recently reported that renal tubular acidosis (RTA) in Sjogren's syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. METHODS: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. RESULTS: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. CONCLUSION: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.

Quality of life improvement and long-term effects of peripheral blood mononuclear cell transplantation for severe arteriosclerosis obliterans in diabetic patients on dialysis.

BACKGROUND: Severe arteriosclerosis obliterans (ASO) can be intractable, especially in diabetic patients on hemodialysis (HD). Recently, the transplantation of autologous peripheral blood mononuclear cells (PBMNCs) has been reported to have beneficial effects, but the long-term effects and impact on quality of life (QOL) have not been studied. METHODS AND RESULTS: Autologous PBMNCs were transplanted into 7 diabetic patients on HD who had severe ASO (5 cases with Fontaine IV and 2 with Fontaine III) after administration of 5 microg/kg granulocyte colony stimulating factor; QOL and degree of ischemia was assessed by measuring skin temperature, skin perfusion pressure (SPP), ankle-brachial index (ABI), and ulcer size, and from angiographic findings. At 4 weeks after the procedure, skin temperature was significantly improved, and SPP and ABI also were increased. These beneficial effects persisted for up to 24 weeks. Angiographic findings and ulcer size improved in 3 of 7 and 3 of 4 patients, respectively. SF-36v2 analysis revealed significant improvements in pain scores. No serious complications were detected. CONCLUSION: Transplantation of PBMNCs resulted in improvement in pain and leg ischemia for over 6 months without serious complications. This therapy is safe and effective for severe ASO in diabetic patients on HD.

Tonsillectomy and corticosteroid therapy with concomitant methylprednisolone pulse therapy for IgA nephropathy.

IgA nephropathy (IgAN) is the most common chronic kidney disease in Japan, but the optimum treatment remains controversial. Our objective was to evaluate the effect of tonsillectomy and corticosteroid therapy combined with methylprednisone pulse therapy in patients at our hospital who had IgAN. Tonsillectomy plus pulse therapy was evaluated in 72 patients (33 men and 39 women) with a diagnosis of IgAN based on renal biopsy who were followed up for more than 1 year. The mean age of the patients was 35.2 +/- 10.9 years (range: 20-58 years) and the mean observation period after tonsillectomy was 20.3 +/- 9.7 months (range: 12-36 months). After tonsillectomy, steroid pulse therapy was administered (methylprednisolone at 500 mg daily for 3 days) 1-3 times and was followed by oral prednisolone from an initial dose of 30 mg on alternate days that was tapered gradually over one year. At 2 years after tonsillectomy, serum creatinine was unchanged or improved in the majority of patients, but worsened in 5 patients. Hematuria (erythrocytes/HPF) improved from Grade 3.76 (11-30/HPF) to Grade 1.94 (1-5/HPF) on average (we defined the grade of hematuria). None of the patients experienced exacerbation of hematuria. Proteinuria decreased from 1.32 g/day to 0.86 g/day (65% of the pretreatment value), and only 4 patients showed an increase of proteinuria. Mean protein loss decreased to less than 0.5 g/day in patients with creatinine clearance > or =90 ml/min and/or patients with initial protein excretion < or =1.0 g/day.

Percutaneous transcatheter hepatic artery embolization for liver cysts in autosomal dominant polycystic kidney disease.

BACKGROUND: We have achieved renal contraction therapy in patients with autosomal dominant polycystic kidney disease (ADPKD) by means of renal transcatheter arterial embolization (TAE) using intravascular coils, decreasing renal size and improving quality of life in almost all patients. We presently perform hepatic TAE in patients with intractable symptomatic polycystic liver. STUDY DESIGN: Uncontrolled trial. SETTING & PARTICIPANTS: 30 patients with ADPKD referred for arteriography to an academic medical center. 22 patients had kidney failure treated by means of dialysis. INTERVENTION: We embolized arteries supplying hepatic segments replaced by cysts that were associated with well-developed hepatic arteries, but obstructed intrahepatic portal veins. OUTCOMES & MEASUREMENTS: Various volumes before and after TAE were compared by using computed tomography and National Institutes of Health Image software in 30 patients with follow-up computed tomography 18 to 37 months after therapy. RESULTS: Total liver volume and total intrahepatic cyst volume decreased from 7,882 +/- 2,916 and 6,677 +/- 2,978 to 6,041 +/- 2,282 and 4,625 +/- 2,299 cm(3), respectively (P < 0.0001 for both). Fractions of remaining (FR) total liver volume and FR of intrahepatic cyst volume were 78.8% +/- 17.6% and 70.4% +/- 20.9%, respectively. Hepatic parenchyma increased from 1,205 +/- 250 to 1,406 +/- 277 cm(3) (P = 0.0004). In 29 of 30 patients, both total liver volume and intrahepatic cyst volume decreased; in 1 patient, total liver volume increased from 5,755 to 7,069 cm(3), whereas cysts enlarged from 4,500 to 5,531 cm(3). No serious complications were experienced. In 24 patients, the post-TAE course was favorable. TAE failed to benefit 6 patients because of unrelated hepatic infection, peritonitis, hepatic failure, acute leukemia, or pelvic fracture. LIMITATIONS: Absence of a control group. CONCLUSIONS: TAE may be an option for patients with ADPKD with symptomatic polycystic liver who are not candidates for surgical treatment.

Renal intravascular large B-cell lymphoma localized only within peritubular capillaries. Report of a case.

We report a 35-year-old Japanese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was referred to our institution for further examination of fever of unknown origin. She had renal dysfunction with a creatinine clearance of 44.1 mL/min, and daily urinary excretion of 0.22 g of protein and 21.5 mg of beta 2 microglobulin. Computed tomography showed markedly enlarged kidneys bilaterally. Percutaneous renal biopsy showed that an island-like atypical lymphoid cell accumulation was encircled with the peritubular capillary walls in many areas of the tubulo-interstitium, resulting in marked destruction of tubular structure. However, almost all the glomeruli were intact. Immunohistochemical analysis confirmed the diagnosis of intravascular large B-cell lymphoma. Shortly after diagnosis, she was treated with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisolone, and her renal function and size improved. Renal involvement by lymphoma has been classified into two categories: intraglomerular intravascular lymphoma and tubulointerstitial diffuse invasion type that is distinct from intravascular lymphoma. For the latter cases with renal dysfunction and marked bilateral nephromegaly but without proteinuria, intravascular lymphoma within intra-peritublar capillaries should be considered as a possible diagnosis.

Systemic AA-amyloidosis related to MPO-ANCA microscopic polyangiitis: a case report.

We report autopsy findings in an 83-year-old woman with myeloperoxidase-type anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis and systemic AA amyloidosis. With a diagnosis of MPO-ANCA-related microscopic polyangiitis, the patient was treated with corticosteroids, but she died of intractable enteritis. Autopsy showed inactive vasculitis affecting small arteries in kidney, lung, intestinal tract, and skeletal muscle. Gastrointestinal viscera were thickened, and AA-amyloid was demonstrated in arterioles and surrounding tissues. Amyloidosis also involved heart, kidney, gallbladder, pancreas, salivary gland, and subcutis. ANCA-positive microscopic polyangiitis appears to have been the likely cause of this patient's AA-amyloidosis.

Successful renal transcatheter arterial embolization in three patients with symptomatic hydronephrosis due to ureteral obstruction.

BACKGROUND: Conventional treatments for symptomatic enlargement of a nonfunctional hydronephrotic kidney caused by obstructive uropathy include surgical treatments. METHODS: Patients included a 67-year-old woman whose obstruction was caused by a lower urinary tract stone complicating spinal tuberculosis (patient 1); a 52-year-old man with compressive complete congenital obstruction crossing the ureteropelvic junction from an aberrant renal artery (patient 2); and a 19-year-old woman with essentially complete idiopathic congenital obstruction at the ureteropelvic junction (patient 3), who required antibiotics for pyelonephritis before embolization. The renal artery was embolized using platinum microcoils. RESULTS: Although the sensation of abdominal fullness diminished within approximately two week after TAE, it took one to two years until the embolized kidney size shrank from 1377+/-634 cm3 (range, 829 to 2072) to 43+/-46 cm3 (42 to 94) by the evaluation of computed tomography. Fever after embolization persisted for 5 days in patient 1, 3 in patient 2, and 9 in patient 3. Flank pain resolved within 5 days in all. Pyelonephritis and complications of treatment have not occurred. CONCLUSION: Embolization for this indication was safe and effective.

Mycosis fungoides in a hemodialysis patient with intractable pruritus.

A 69-year-old Japanese man developed pruritus 3 years after beginning hemodialysis. Although eczema was not apparent at first, erythematous patches and plaques developed gradually on the affected skin. Secondary hyperparathyroidism was considered to be a main cause of this patient's pruritus, but skin lesions worsened even after parathyroidectomy had markedly decreased parathyroid hormone concentrations. Two months later, he developed an antibiotic-refractory fever of unknown origin and cervical, axillary, and inguinal lymphadenopathy. Elevations of soluble interleukin-2 receptor with 7410 U/mL and IgE with 24 600 U/mL in serum were noted, as was eosinophilia. The skin showed multiple slightly scaly patches and infiltrative plaques, which were reddish brown and distributed widely over the body surface except for the scalp and face. Mycosis fungoides, a cutaneous T-cell lymphoma, was diagnosed from biopsy specimens findings in skin and lymph node. Mycosis fungoides has not been documented as a cause of pruritus in hemodialysis patients. However, if skin lesions steadily worsen in hemodialysis patients, malignant diseases such as mycosis fungoides should be considered.

Outcome and treatment of bucillamine-induced nephropathy.

BACKGROUND: Bucillamine (BCL), a treatment for rheumatoid arthritis, occasionally causes proteinuria. Renal specimens are reported to show segmental granular deposition of immunoglobulin G, associated with membranous nephropathy. Long-term course and optimal treatment have remained unknown, and were investigated here. METHODS: We examined clinical records of 400 patients treated with BCL for rheumatoid arthritis, at our hospital from 1998 to 2003, finding 17 with proteinuria and biopsy-proven BCL-induced nephropathy. RESULTS: In all 17 patients, proteinuria resolved without loss of renal function between 3 and 85 months after discontinuing BCL (14.1 +/- 3.4). The only factor influencing time to remission was pathologic stage of membranous nephropathy (stage I vs. stage II or III: 11.5 +/- 4.8 vs. 21.6 +/- 3.3 months; p = 0.02). Maximal proteinuria, total amount of BCL, BCL exposure time, and use of prednisolone or other immunosuppressant agents did not significantly influence time until remission. CONCLUSION: The most important therapeutic step in treating BCL-induced nephropathy is to discontinue BCL. Prednisolone or other immunosuppressant agents might not be effective.

[Case of autosomal dominant polycystic kidney disease associated with pelvic insufficiency fracture].

We experienced a case of A-59-year-old woman having autosomal dominant polycystic kidney disease with renal insufficiency associated with pelvic insufficiency fracture. On admission the pelvic bone compressed by the enlarged kidney and liver due to polycystic disease was demonstrated on the pelvic CT. Her bone mineral density was not significantly decreased contrary to our expectation. The prominent bone absorption in the endosteal and exosteal surface of the cortical bone was demonstrated in the bone specimen form iliac bone although the state of the cancellous bone and bone formation rate was normal. We performed the transcatheter embolization (TAE) to the kidney and liver to diminish their sizes. The fracture was rapidly improved and she could walk 6 months later after the TAE. In this case, we considered that the longstanding compression to the pelvic bone by the enlarged liver and kidney made the cortical and the binding of muscle/tendon and cortical bone fragile and it led to the pelvic insufficiency fracture.

Pelvic insufficiency fracture related to autosomal dominant polycystic kidney disease.

We report the case of a patient with autosomal dominant polycystic kidney disease (ADPKD) and an insufficiency-type fracture of the pelvis. A 60-year-old Japanese woman was admitted because of pain in the right ischium and pubis that began suddenly with no precipitating cause. Computed tomography showed the bony pelvis to be compressed by enlarged dependent kidneys and an enlarged liver. We relieved compression on the pelvic bones by means of transarterial embolization (TAE) to the kidneys and liver after initiation of hemodialysis therapy. The fracture healed gradually after TAE, and the patient could walk 4 months later. In an iliac bone specimen obtained before TAE, cancellous bone was intact, but periosteal and endosteal surfaces of cortical bone showed marked resorption and were irregular. Normally, many ligaments are connected tightly to the periosteal surface, supporting the cortical bone. However, because of extensive surface resorption associated with pressure from enlarged kidneys, connections between ligaments and the periosteal surface presumably became fragile, promoting an insufficiency fracture from unapparent external forces. Thus, ADPKD is a potential cause of insufficiency fracture owing to abnormalities of cortical bone.