Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with chronic kidney disease (CKD), including those undergoing haemodialysis (HD). METHODS: This retrospective cohort study included 425 patients with RA prescribed their first bDMARDs at two hospitals from 2004 to 2021. Patients were categorised by kidney function and bDMARD modality (TNFα inhibitors (TNFαis), interleukin-6 inhibitors (IL-6is), cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4-Ig)). The primary outcome was the 36-month drug retention rate, with secondary outcomes including changes in Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate (ESR), prednisolone dosage and reasons for discontinuation. RESULTS: The 36-month drug retention rates by estimated glomerular filtration rate (eGFR) (≥60, 30-60, <30 mL/min/1.73 m2) were as follows: all bDMARDs (45.2%, 32.0%, 41.4%), TNFαis (45.3%, 28.2%, 34.0%), IL-6is (47.4%, 66.7%, 71.4%) and CTLA-4Ig (50.0%, 31.3%, 33.3%). Even in groups with lower kidney function, the drug retention rate of bDMARDs was generally maintained. However, the retention rate of TNFαis was significantly lower in patients with eGFR <30 mL/min/1.73 m2. IL-6is showed the highest retention rate and the lowest discontinuation rate due to ineffectiveness in this group (HR 0.11, 95% CI 0.02 to 0.85, p=0.03). All bDMARDs improved DAS28-CRP/ESR and reduced prednisolone dosage across all groups. CONCLUSION: bDMARDs demonstrated effective and safe profiles in patients with RA with CKD, even among patients on HD. In particular, IL-6is had a significantly higher drug retention rate in patients with an eGFR of <30 mL/min/1.73 m2 and fewer discontinuations due to ineffectiveness. IL-6is were more efficacious as monotherapy compared with the other bDMARDs.

A Case of Autosomal Dominant Polycystic Kidney Disease With Resolution of Massive Pericardial Effusion After Renal Transcatheter Artery Embolization.

A 68-year-old woman being treated with hemodialysis for autosomal dominant polycystic kidney disease was admitted for progressive dyspnea over 6 months. On chest radiography, her cardiothoracic ratio had increased from 52.2% 6 months prior, to 71%, and echocardiography revealed diffuse pericardial effusion and right ventricular diastolic insufficiency. A resultant pericardial tamponade was thought to be the cause of the patient's dyspnea, and therefore a pericardiocentesis was performed, with a total of 2,000mL of fluid removed. However, 21 days later the same amount of pericardial fluid had reaccumulated. The second pericardiocentesis was performed, followed by transcatheter renal artery embolization (TAE). The kidneys, which were hard on palpation before TAE, softened immediately after TAE. After resolution of the pericardial effusion was confirmed, the patient was discharged after 24 days in hospital. Twelve months later, the patient was asymptomatic, the cardiothoracic ratio decreased to 48% on chest radiography and computed tomography revealed no reaccumulation of pericardial effusion. This case illustrates a potential relationship between enlarged kidneys in autosomal dominant polycystic kidney disease and pericardial effusion.

Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

BACKGROUND: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version. METHODS AND RESULTS: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. CONCLUSIONS: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder after kidney transplantation: A case report.

We report on a 53-year-old Japanese man diagnosed with gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder (B-PTLD) after endoscopy for gastric discomfort 28 months after the patient underwent renal transplantation in Ethiopia. Serum Epstein-Barr virus (EBV) tests were negative before transplantation, but the tumor cells collected from a gastric biopsy showed positive EBV-encoded small RNAs (EBER) at B-PTLD onset. Intensive treatment started with R(rituximab)-CHOP therapy and continued with DA-EPOCH-R therapy has been effective, and relapse has not yet occurred. Burkitt lymphoma has a poor prognosis, but B-PTLD may be effectively treated with high-dose chemotherapy. This is a rare case of gastric B-PTLD in a Japanese patient.

Digital whole-slide imaging of changes in amyloid after peripheral blood stem cell transplantation in patients with amyloid light-chain amyloidosis.

Peripheral blood stem cell transplantation (PBSCT) has made amyloid light-chain (AL) amyloidosis treatable. After PBSCT, hematological complete remission (HCR) can be achieved, leading to improved renal prognosis. The purpose of this study was to evaluate whether whole slide imaging of biopsy samples shows a post-treatment reduction in amyloid deposits in patients with AL amyloidosis. Patients were divided into three groups: Group A (n = 8), not eligible for PBSCT and treated with other therapies; Group B (n = 11), treated with PBSCT and achieved HCR; and Group C (n = 5), treated with PBSCT but did not achieve HCR. Clinical findings and amyloid deposition in glomeruli, interstitium, and blood vessels were compared before and after treatment using digital whole-slide imaging. Proteinuria and hypoalbuminemia improved more in Group B than in the other groups, and in Group B, amyloid deposition improved more in the glomeruli than in the interstitium and blood vessels. The long-term renal and survival prognosis was better in Group B than in the other groups. PBSCT can be expected to improve long-term clinical and renal histological prognosis in patients with AL amyloidosis who achieve HCR. Amyloid disappearance from renal tissue may take a long time even after clinical HCR.

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography and computed tomography for differentiating polymyalgia rheumatica and rheumatoid arthritis: Using classification and regression tree analysis.

OBJECTIVES: Determining which sites were important to differentiate polymyalgia rheumatica (PMR) from rheumatoid arthritis (RA) using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET-CT) is challenging. METHODS: Patients with PMR or RA who were undergoing PET-CT were recruited at two mutual-aid hospitals in Japan between 2009 and 2018. Classification and regression tree (CART) analyses were performed to identify FDG uptake patterns that differentiated PMR from RA. RESULTS: We enrolled 35 patients with PMR and 46 patients with RA. Univariate CART analysis showed that FDG uptake in the shoulder joints, spinous processes of the lumbar vertebrae, pubic symphysis, sternoclavicular joints, ischial tuberosities, greater trochanters, and hip joints differentiated PMR from RA. Multivariate CART analysis revealed that FDG uptake by at least one of the ischial tuberosities had the highest diagnostic value for distinguishing PMR from RA (sensitivity, 77.1%; specificity, 82.6%). We performed the same CART analysis to patients who had not undergone treatment (PMR, n = 28; RA, n = 9). Similar results were obtained, and sensitivity and specificity were increased (sensitivity, 89.3%; specificity, 88.8%). CONCLUSIONS: In PET-CT, FDG uptake by at least one of the ischial tuberosities best discriminates between PMR and RA.

Relationship between MRI findings and renal histopathology in IgG4-related tubulointerstitial nephritis.

BACKGROUND: MRI is expected to be a valuable tool for evaluating disease activity in immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis (IgG4-TIN). However, the correlation between MRI findings and renal histopathological findings remains to be elucidated. PURPOSE: This study aimed to clarify the correlation between MRI findings and renal histopathological findings in IgG4-TIN. METHOD: This retrospective cross-sectional study investigated 26 patients with biopsy-proven IgG4-TIN who underwent simultaneous percutaneous kidney biopsies and abdominal MRI examinations at Toranomon Hospital or Toranomon Hospital Kajigaya between December 2007 and November 2022. We reviewed kidney biopsy specimens and scored the degree of inflammatory cell infiltration and interstitial fibrosis. We assessed abdominal MRI, specifically examining T1WI, T2WI, and DWI, for the presence of abnormal signals in the inferior pole of the kidney on the side where the kidney biopsy was performed. Spearman's correlation coefficient test was conducted to examine the relationship between the images and histological findings. RESULT: For T1WI, eight cases showed a positive low-intensity signal, and 18 cases were negative. For T2WI, 19 cases were positive for a low-intensity signal, and seven cases were negative. In DWI, 23 cases were positive for a high-intensity signal, and one was negative. T1WI low-intensity signal and T2WI low-intensity signal were significantly correlated with interstitial fibrosis score (correlation coefficient 0.52 and 0.64). DWI revealed IgG4-TIN detected IgG4-TIN lesions with the highest sensitivity; however, the correlation with inflammatory cell infiltration score was not significant. CONCLUSION: Low-intensity signal on T2WI is useful for predicting the degree of fibrosis in IgG4-TIN.

Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study.

BACKGROUND: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45-63) years; 62.6% men; Hb 13.3 (12.0-14.5) g/dL; eGFR 76.2 (66.6-88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100-1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed. RESULTS: Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = -0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26-5.97], 2.33 (95% CI 1.07-5.75) and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS: Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.

Dialysis-related carpal tunnel syndrome in the past 40 years.

PURPOSE AND METHOD: Patients on hemodialysis develop carpal tunnel syndrome (CTS) due to an accumulation of dialysis-related ß2 microglobulin (ß2m) amyloid (DRA). In Japan, dialysis technology has progressed remarkably in the past 40 years and has increased the time until patients require surgery for CTS. However, unclear is whether the time from the start of hemodialysis to the first surgery for CTS is associated with ß2m clearance by the different hemodialysis techniques. Therefore, we retrospectively evaluated ß2m clearance, serum ß2m levels, and the change in the length of this period in patients across 4 periods according to the year that first surgery for CTS was performed: period 1, 1982-1989; period 2, 1990-1999; period 3, 2000-2009; and period 4, 2010-2019. RESULT: A total of 222 patients who met the selection criteria were included. Mean ß2m clearance was -1.8 ± 16.7% in period 1, and improved to 65.4 ± 8.6% in period 3. Accordingly, the serum ß2m value after hemodialysis decreased significantly. The time from the start of hemodialysis to the first surgery for CTS was 12.4 ± 2.9 years in period 1 but increased to 21.8 ± 6.3 years in period 3. In multivariable linear regression analysis, the significant factors contributing to ß2m clearance were periods 2, 3, and 4. In particular, the relation between removal of ß2m and the extension of the dialysis vintage in period 1 and 2 was remarkable compared with periods 3 and 4. CONCLUSION: Our findings indicate that improvement of ß2m clearance via advances in dialysis technology might result in a significant extension in the time between starting HD and the first surgery for CTS.

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis.

BACKGROUND AND PURPOSE: We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA). METHODS: We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990-1999 (n = 48); period 2, 2000-2009(n = 57); period 3, 2010-2019 (n = 51). RESULTS: Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010-2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1-3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time. CONCLUSION: Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA.

Hypocalcemia and bone mineral changes in hemodialysis patients with low bone mass treated with denosumab: a 2-year observational study.

BACKGROUND: Increases in bone mineral density (BMD) following a single dose of denosumab and increased incidence of denosumab-associated acute hypocalcemia (DAAH) have been reported in chronic kidney disease patients. Little is known about clinical risk factors related to DAAH and the long-term effect of denosumab on BMD in hemodialysis patients. METHODS: An observational noncontrolled study involving 47 hemodialysis patients was conducted to determine the independent risk factors related to percentage changes in serum calcium (Ca) levels associated with denosumab using multivariate regression analysis. Optimal predictive markers for DAAH were explored by receiver operating characteristic analysis. Percentage changes of BMD at the lumbar spine (LS) and femoral neck (FN) at 24 months were investigated. RESULTS: The incidence of DAAH [serum corrected Ca (cCa) ≤8 mg/dL] following denosumab was 25.5%. Multivariate regression analysis showed that baseline bone alkaline phosphatase was independently related to percentage changes in cCa levels (ß = -0.407, P = 0.008). Tartrate-resistant acid phosphatase-5b was found to be the most accurate marker to predict DAAH, with an area under the curve of 0.750 (95% confidence interval 0.546-0.954; P = 0.02), and the optimal cut-off level was 670 mU/mL with sensitivity: 0.727 and specificity: 0.733. BMD significantly increased by 5.9 ± 1.7% (P = 0.01) at LS and 4.2 ± 1.5% (P = 0.04) at FN at 24 months. CONCLUSIONS: In hemodialysis patients, high bone turnover was an independent risk factor for the Ca declines induced by denosumab. Denosumab significantly increased BMD at LS and FN at 24 months.

Tocilizumab preserves renal function in rheumatoid arthritis with AA amyloidosis and end-stage kidney disease: Two case reports.

Case 1: A 59-year-old Japanese woman with rheumatoid arthritis (RA) for 36 years was admitted for evaluation of deteriorating renal function. Her serum creatine was 4.2 mg/dL, and proteinuria was 6.5 g daily. Renal and duodenal biopsy revealed AA amyloidosis. After treatment with tocilizumab (a humanized anti-interleukin-6 receptor antibody), proteinuria decreased to 1.1 g daily. The patient's renal function subsequently remained stable for 8 years. Case 2: A 71-year-old Japanese man with RA for 30 years was admitted due to deterioration of renal function. Serum creatine was 2.9 mg/dL, and urinary protein excretion was 0.06 g daily. Renal and duodenal biopsy identified AA amyloidosis. Tocilizumab was initiated, and his renal function remained stable for 6 years. The 2nd duodenal biopsy showed a marked decrease of AA amyloid deposits. Conclusion: These two cases suggest that tocilizumab may preserve renal function in the setting of end-stage kidney disease and shift the point of no return for RA patients with AA amyloidosis and renal dysfunction.

Syphilis-associated membranous nephropathy successfully treated with amoxicillin.

A 33-year-old Japanese man with no significant past medical history was admitted to our hospital for evaluation of weight gain and pitting edema. A laboratory test confirmed nephrotic-range proteinuria. Renal biopsy showed subepithelial deposits, and membranous nephropathy (MN) was diagnosed. Closer examination clarified an active syphilis infection. After renal biopsy, we prescribed amoxicillin for 8 weeks to treat the syphilis infection. Three weeks later, the patient's proteinuria dramatically decreased. This case is of interest because syphilis can become a cause of acute-onset MN in younger adults, and the incidence of syphilis is increasing in Japan.
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A case of thrombotic microangiopathy associated with polymyositis.

A 60-year-old Japanese woman with polymyositis (PM) developed hemolytic anemia (hemoglobin of 7.3 g/dL), thrombocytopenia (platelet of 9.1×104/µL), and acute kidney injury (Cre of 4.7 mg/dL) at 14 days after starting steroid therapy. Renal biopsy revealed glomerular endothelial swelling with fibrin thrombi and fragmented erythrocytes in the capillary lumens. Hemolytic uremic syndrome (HUS) with thrombotic microangiopathy (TMA) was diagnosed. Hemodialysis and plasma exchange/plasma transfusion were initiated, but HUS did not subside. After 45 days, the patient died of hemorrhagic respiratory failure. Autopsy showed fibrin thrombi filling the glomerular vascular pole and the small arteries in most glomeruli, resulting in glomerular collapse and glomerular basement membrane (GBM) duplication. Although renal involvement by PM is rare, HUS/TMA should be remembered as one of the serious renal complications of PM.

Case report: Osteomalacia due to bisphosphonate treatment in a patient on hemodialysis.

BACKGROUND: No publications have reported on osteomalacia in patients receiving intermittent cyclical therapy with etidronate (a bisphosphonate) and undergoing long-term hemodialysis (HD). CASE PRESENTATION: We report on a 46-year-old Japanese man admitted to our hospital for further examination of left forearm pain. Maintenance HD was started at age 24 years, and the man had been on HD since then. At age 38 years, surgical parathyroidectomy was performed for secondary hyperparathyroidism; iliac crest bone biopsy performed at the same time showed osteitis fibrosa. The active vitamin D3 preparation calcitriol was started, and intermittent cyclical etidronate therapy was introduced 2 years later for osteoporosis. At age 45 years, the patient stopped taking calcitriol because of hypercalcemia but continued with etidronate. At age 46 years, a pseudofracture with a Looser zone occurred in the left ulna, and left femur bone biopsy revealed osteomalacia. Etidronate was discontinued, and calcitriol was restarted; open reduction and internal fixation with an angular stability plate were performed. Union of the bone was achieved 10 months after the operation. At age 49 years, a lumber bone biopsy confirmed improved bone morphometry. CONCLUSIONS: We believe that intermittent cyclical etidronate therapy without administration of active vitamin D3 during long-term HD might have induced osteomalacia, resulting in the ulna insufficiency fracture. Therefore, we propose that administration of active vitamin D3 is essential to prevent osteomalacia in patients on long-term HD who are receiving bisphosphonates and have potential vitamin D3 deficiency.

Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Tolvaptan is the only therapeutic drug for autosomal dominant polycystic kidney disease (ADPKD). The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature. METHODS: We retrospectively evaluated the relationship between genotype and the efficacy of tolvaptan in 18 patients with ADPKD who had been treated at Toranomon Hospital and undergone genetic testing between April 2016 and February 2020. RESULTS: The annual change in estimated glomerular filtration rate (ΔeGFR/y) from before to after tolvaptan was from a median of -5.5 to -2.5 mL/min/1.73 m2 in the PKD1 truncating group, -3.3 to -2.4 mL/min/1.73 m2 in the PKD1 non-truncating group, -3.1 to -1.6 mL/min/1.73 m2 in the PKD2 group, and -1.9 to -2.6 mL/min/1.73 m2 in the group with no PKD1/2 mutation. The median degrees of improvement of ΔeGFR/y were 2.5 (45%), 0.4 (10%), 0.6 (28%), and -0.7 (-37%) mL/min/1.73 m2, respectively. Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in ΔeGFR/y with tolvaptan (0.6 vs. -0.7 mL/min/1.73 m2, respectively; p = 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (-6.7 vs. -1.1%, respectively; p = 0.02). CONCLUSION: Patients with ADPKD and no PKD1/2 mutation showed less improvement in ΔeGFR/y and the annual rate of increase in TKV with tolvaptan. Detecting PKD1/2 mutations may be useful for predicting the effectiveness of tolvaptan.

How to resolve confusion in the clinical setting for the diagnosis of heterozygous COL4A3 or COL4A4 gene variants? Discussion and suggestions from nephrologists.

Both thin basement membrane nephropathy (TBMN) and autosomal dominant Alport syndrome (ADAS) are types of hereditary nephritis resulting from heterozygous mutations in COL4A3 or COL4A4 genes. Although TBMN is characterized by hematuria and thinning of the glomerular basement membrane (GBM) with excellent renal prognosis, some patients develop end-stage renal disease (ESRD) later in life. In contrast, although AS is characterized by progressive nephropathy with lamellation of the GBM, there are some patients diagnosed with ADAS from a family history of ESRD but who only suffer from hematuria with GBM thinning. These findings indicate a limitation in distinction between TBMN and ADAS. Diagnosis of AS is significant because it facilitates careful follow-up and early treatment, whereas diagnosis of TBMN can underestimate the risk of ESRD. However, some experts are against using the term ADAS as the phenotypes of heterozygous variants vary from no urinary abnormality to ESRD, even between family members with the same mutations, indicating that unknown secondary factors may play a large role in the disease severity. These diagnostic difficulties result in significant confusion in clinical settings. Moreover, recent studies revealed that the number of patients with chronic kidney disease caused by these gene mutations is far higher than previously thought. The aim of this article is to review differing opinions regarding the diagnosis of heterozygous COL4A3 or COL4A4 variants, and to highlight the importance for nephrologists to recognize this disease, and the importance of the need to reclassify this disease to minimize the current confusion.

Relevance of concurrent hypercalcemia in ureteric sarcoidosis complicated with bladder urothelial carcinoma: a case report.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disorder and can affect any organ; however, ureteric involvement is extremely rare with only four cases reported in the literature to date, all of which were diagnosed with surgical ureteral resection including a nephroureterectomy. This study reports the first case of ureteric sarcoidosis controlled with medical therapy where a differential diagnosis was performed based on the diagnostic clue of hypercalcemia. A definitive diagnosis was established without surgical resection of the ureter. CASE PRESENTATION: A 60-year-old man presented with anorexia and weight loss. Blood tests showed renal dysfunction and hypercalcemia. Computed tomography revealed left hydronephrosis associated with left lower ureteral wall thickening, which showed high signal intensity on diffusion-weighted magnetic resonance imaging. Similarly, we detected a bladder tumor on cystoscopy, and a 2-cm-long stenosis was revealed by retrograde ureterography; therefore, ureteral cancer was suspected. Meanwhile, considering the clinical implication of hypercalcemia, a differential diagnosis of sarcoidosis was established based on elevated levels of sarcoidosis markers. Fluorodeoxyglucose positron emission tomography showed fluorodeoxyglucose accumulation in the left lower ureter, skin, and muscles, suggestive of ureteric sarcoidosis with systemic sarcoid nodules. For a definitive diagnosis, transurethral resection of the bladder tumor and ureteroscopic biopsy were performed. Histopathological examination revealed ureteric sarcoidosis with bladder urothelial carcinoma. Following an oral administration of prednisolone, hypercalcemia instantly resolved, the renal function immediately improved, and the left ureteral lesion showed complete resolution with no recurrence. CONCLUSIONS: In this case, the co-occurrence of ureteral lesion with bladder tumor evoked a diagnosis of ureteral cancer. However, considering a case of ureteral lesion complicated with hypercalcemia, assessment for differential diagnosis was performed based on the calcium metabolism and sarcoidosis markers. In cases of suspected ureteric sarcoidosis from the assessment, pathological evaluation with ureteroscopic biopsy should be performed to avoid nephroureterectomy.

Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History.

BACKGROUND: Genetic characteristics of polycystic kidney disease (PKD) patients without apparent family history were reported to be different from those with a positive family history. However, the clinical course of PKD patients with no apparent family history is not well documented in the literature. METHODS: We evaluated the relationship between genotype and the clinical course of 62 PKD patients with no apparent family history. RESULTS: The annual decline of renal function was faster in the patients with PKD1/PKD2 mutation (PKD1 truncating [-3.08; 95% CI -5.30 to -0.87, p = 0.007], PKD1 nontruncating [-2.10; -3.82 to -0.38, p = 0.02], and PKD2 [-2.31; -4.40 to -0.23, p = 0.03]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, estimated glomerular filtration rate (eGFR), height-adjusted total kidney volume (TKV), and mean arterial pressure (MAP). There was no significant difference in the annual decline of renal function among the different PKD1/PKD2 groups, but Kaplan-Meier analysis showed that progression to eGFR < 15 mL/min/1.73 m2 was significantly faster in PKD1 truncating group (p = 0.05). The annual rate of TKV increase was larger in the patients with PKD1/PKD2 mutation (PKD1 truncating [4.63; 95% CI 0.62-8.64, p = 0.03], PKD1 nontruncating [3.79; 0.55-7.03, p = 0.02], and PKD2 [2.11; -1.90 to 6.12, p = 0.29]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, eGFR, and MAP. CONCLUSION: Detection of PKD1/PKD2 mutation, especially PKD1 truncating, is useful for predicting the renal outcome and rate of TKV increase in PKD patients with no apparent family history.

Significance of urinary albumin excretion in patients with cast nephropathy
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BACKGROUND: This study was performed to determine whether the urinary albumin excretion rate (%UAE) could distinguish myeloma cast nephropathy (MCN) without glomerular amyloid deposition from MCN with glomerular amyloid deposition. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data on 16 patients with MCN diagnosed by renal biopsy at Toranomon Hospital from 2004 to 2014. RESULTS: A total of 10 patients had pure MCN without glomerular amyloid deposition (group 1), and 6 patients had MCN with glomerular amyloid deposition (group 2). In all 10 patients from group 1, the underlying disease was multiple myeloma (MM), while 4 patients had MM, and 2 patients had lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in group 2. Total protein did not show a significant difference between the two groups, but serum albumin was significantly higher in group 1 than group 2 (p = 0.0101). Serum-adjusted calcium did not show a significant difference between the groups, while serum creatinine (Cre) was significantly higher in group 1 than group 2 (p = 0.0343). Although urinary protein excretion did not differ significantly between the groups, the %UAE was significantly lower in group 1 than group 2 (p = 0.00198). In group 2, 3 of the 4 patients with MM died within 15 months of diagnosis, but the 2 patients with LPL/WM are alive after 32 months. In group 1, only 1 patient died (of unknown causes) within 15 months after diagnosis. CONCLUSION: In patients with MCN, %UAE may be a useful marker for the detection of coexistence of glomerular lesions, such as amyloidosis, which are associated with a poor outcome.