Repetitive Refractory Renal Cyst Infection in Autosomal Dominant Polycystic Kidney Disease for which Renal Transcatheter Arterial Embolization Was Effective in Preventing Recurrence.

Renal cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often difficult to treat and can be fatal. While nephrectomy is the standard therapy for severe refractory renal cyst infection, it can be associated with severe adverse events. We experienced a case of repetitive renal cyst infection in a 58-year-old Japanese man with ADPKD on dialysis. He underwent renal transcatheter arterial embolization (TAE) four months after the last episodes of renal cyst infection, and his renal cyst infection has not recurred since renal TAE. This case suggested that renal TAE is effective for preventing repetitive renal cyst infection.

Efficacy of Secukinumab for Plaque Psoriasis in a Patient on Hemodialysis.

Secukinumab is effective to treat plaque psoriasis. However, the safety and efficiency of secukinumab have not been clarified in patients on hemodialysis. We report a 60-year-old Japanese woman. Plaque psoriasis was diagnosed at the age of 25 years and hemodialysis was started at the age of 39 years. Her skin lesions persisted despite use of topical agents such as maxacalcitol and betamethasone. Accordingly, administration of secukinumab was started at a dose of 150 mg. The psoriasis area and severity index (PASI) score decreased from 49.8 to 14.8 after 2 weeks and to 0 after 6 weeks, with remission being maintained after 28 months. No adverse reactions were seen. This case indicates that secukinumab may be effective for severe psoriasis in patients on hemodialysis for end-stage renal disease.

Increase of 1,25 dihydroxyvitamin D in sarcoidosis patients with renal dysfunction.

INTRODUCTION: In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction. MATERIALS AND METHODS: We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). RESULTS: Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients. CONCLUSION: While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.

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.

The efficacy and safety of anti-interleukin-6 receptor monoclonal blockade in a renal transplant patient with Castleman disease: early post-transplant outcome.

BACKGROUND: Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disease characterized by systemic inflammatory reactions associated with the dysregulated production of interleukin-6 (IL-6). In patients with MCD, renal involvement is uncommon, with only one report published regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to MCD. Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown. CASE PRESENTATION: Herein, we describe the case of a 50-year-old man with MCD who received living-donor KTx for ESRD. Post-operative immunosuppression consisted of a triple-drug regimen (tacrolimus, mycophenolate mofetil and methylprednisolone) with TCZ that was administered intravenously every 2 weeks. At 17 months post-transplantation, the patient remains asymptomatic, and the allograft pathology has shown no evidence of rejection and no development of de novo donor-specific antibody (DSA). CONCLUSIONS: To our knowledge, this is the second reported case of an MCD patient with ESRD who underwent successful KTx. TCZ safely supported the patient during the perioperative period, and this drug may be useful for blocking the generation of donor-specific antibodies and reducing the risk of rejection episodes. KTx in combination with TCZ is thus considered a viable treatment option for ESRD due to MCD.

Tolvaptan in Japanese patients with later-stage autosomal dominant polycystic kidney disease.

BACKGROUND: A recent study demonstrated that tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in later-stage autosomal dominant polycystic kidney disease (ADPKD) patients. However, Japanese patients were not included in that trial, therefore tolvaptan's efficacy in Japanese patients with advanced chronic kidney disease (CKD) has remained unknown. METHODS: In this prospective cohort study, 54 patients with ADPKD who had eGFR ≥ 15 ml/min/1.73 m2 and total kidney volume (TKV) ≥ 750 ml were treated with tolvaptan. The primary endpoint was the change in height-adjusted total kidney volume (htTKV) and eGFR after 1-year treatment with tolvaptan. Then, we compared the primary endpoint between later CKD stage (baseline eGFR < 45 ml/min/1.73 m2) and earlier CKD stage (baseline eGFR ≥ 45 ml/min/1.73 m2). RESULTS: The rate of kidney growth during the 1-year treatment did not differ significantly between earlier and later CKD stages. The median and interquartile range of relative change in htTKV in later CKD stage was 8.2%/year [4.4, 26.6], as compared with 5.7%/year [1.6, 16.4] in earlier CKD stage (p = 0.17). Nor did the rate of eGFR decline between earlier and later CKD stages. The relative annual change in eGFR in later CKD stage was - 9.7%/year [- 15.9, - 2.1], as compared with - 6.8%/year [- 11.1, 0.1] in earlier CKD stage (p = 0.18). CONCLUSION: This analysis indicates that the efficacy of tolvaptan for Japanese patients with later stage ADPKD was not significantly different from that of Japanese patients with earlier stage ADPKD.

Renal-limited Cryoglobulinemic Vasculitis: Two Case Reports.

Cryoglobulinemic vasculitis (CV) presents with systemic manifestations, including renal disease, arthritis, peripheral neuropathy, and muscle weakness. We encountered two patients who developed severe nephrotic range proteinuria; however, extrarenal manifestations were not noted during the clinical course. A renal biopsy revealed typical membranoproliferative glomerulonephritis (MPGN) with huge thrombus-like endothelial deposits and predominant IgM positivity, but electron microscopy did not reveal any definite microtubules. Immunosuppressive therapy and plasmapheresis were only partially effective, and the improvement was not durable. Biological therapy with rituximab (RTX) had no effect. Renal-limited CV should be recognized as a subset of essential CV.

Transcatheter Arterial Embolization Therapy for Huge Renal Cysts: Two Case Reports.

We encountered 2 patients with symptomatic huge simple renal cysts. In case 1, 4,000 mL of cyst fluid was drained via a catheter, but intracystic bleeding occurred immediately afterwards. Transcatheter arterial embolization (TAE) was performed, after which the bleeding stopped, and cyst drainage was repeated successfully. After 2 years, the total cyst volume was reduced from 11,775 mL to 75.4 mL. In case 2, TAE was performed prophylactically before drainage. Subsequently, 9,400 mL of fluid was removed from multiple cysts. After 1 year, the total cyst volume was reduced from 9,215 mL to 633 mL without bleeding. Based on these 2 cases, prophylactic TAE before drainage may be useful in patients with huge renal cysts.

Microscopic polyangiitis necrotizing glomerulonephritis associated with pregnancy: case with a 20-year clinical course and review of the literature.

A 29-year-old woman with past medical history of hypertension was referred to our hospital for the evaluation of kidney dysfunction (serum creatinine 1.0 mg/dL), proteinuria (0.54 g/gCre), and microscopic hematuria. Renal biopsy before the first pregnancy was supportive for benign nephrosclerosis with no evidence of vasculitis. After her second pregnancy and delivery when she was 32 years old, she developed proteinuria of 3.2 g/gCre, hematuria, and elevated serum creatinine level of 2.6 mg/dL. Second renal biopsy revealed necrotizing glomerulonephritis and her serum MPO-ANCA was positive, leading to the diagnosis of MPA/renal-limited vasculitis (RLV). Interestingly, frozen preserved serum from 4 years earlier also tested positive for MPO-ANCA. Despite intensive treatment, hemodialysis was required 10 years later due to progressive deterioration of renal function. At that time, she developed pericarditis, bloody cardiac tamponade, and pulmonary alveolar hemorrhage, resulting in a diagnosis of systemic vasculitis MPA. She received living donor kidney transplantation at the age of 44 years, after which serum creatinine has been stable around 1.1 mg/dL without proteinuria or hematuria and MPO-ANCA has remained negative. The association of vasculitis with pregnancy and delivery is not well documented, especially in patients with MPA. Here, we report this MPO-ANCA positive woman developing MPA necrotizing glomerulonephritis after her second pregnancy and a 20-year clinical course.

Renal histology in a patient with TAFRO syndrome: a case report.

An 84-year-old Japanese man was admitted due to anasarca, thrombocytopenia, systemic inflammation, and progressive renal insufficiency, resistance to diuretics, glucocorticoid therapy, and plasma exchange. Renal biopsy showed diffuse endocapillary proliferation and mesangiolysis without any immune deposits. Tocilizumab suppressed systemic inflammation, resulting in improvement of anasarca and renal dysfunction, but thrombocytopenia persisted and platelet-associated IgG antibody was elevated. Although romiplostim was effective for thrombocytopenia, the patient died of aspiration pneumonia after cerebral hemorrhage. Autopsy showed hyaline vascular-type Castleman disease-like lymphadenopathy and reticulin myelofibrosis with an increase of megakaryocytes. Renal finding showed that endocapillary injury improved, and collapsed glomeruli were noted. This patient fitted the criteria for TAFRO (thrombocytopenia [T], anasarca [A], fever [F], reticulin myelofibrosis [R], and organomegaly [O]) syndrome. The clinical course suggests that 2 factors, including overproduction of interleukin 6 and autoimmune-mediated thrombocytopenia via thrombopoietin receptor, may have contributed to the pathogenesis of TAFRO syndrome in this patient.

Tolvaptan for the Treatment of Enlarged Polycystic Liver Disease.

A 44-year-old Japanese woman with autosomal dominant polycystic kidney disease was admitted to our hospital for evaluation of abdominal distension. Her eGFR was 53.7 mL/min/1.73 m2. Total kidney volume was 2,614 mL. Tolvaptan (60 mg/day) was started to treat renal involvement. The patient's abdominal fullness began to improve and liver volume, indicating advanced polycystic liver disease (PLD), decreased from 9,750 mL to 8,345 mL after 17 months of tolvaptan treatment, though there was no significant change in kidney volume. This case indicates that tolvaptan may be a therapeutic option for hepatomegaly in patients with symptomatic PLD.

Sjögren Syndrome-Related Membranous Glomerulonephritis Progressing to Membranoproliferative Glomerulonephritis.

We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis.