A case of malignant nephrosclerosis occurring with serum renin in the normal range.

A 37-year-old Japanese man was admitted to our hospital for evaluation of severe hypertension and visual impairment. His serum creatinine was 4.16 mg/dL. Plasma renin activity was normal (2.7 ng/mL/h), but plasma aldosterone concentration was elevated (27.2 ng/dL). A kidney biopsy showed concentric subendothelial edematous thickening of the arterioles (onion skin pattern) with luminal narrowing or obstruction, and malignant nephrosclerosis was diagnosed. Antihypertensive therapies, including an angiotensin II receptor blocker and spironolactone, were administered and effectively preserved kidney function and normalized blood pressure. This case indicates that hyperaldosteronemia in the presence of normal renin levels might also cause malignant hypertension.

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.

Autosomal Dominant Polycystic Kidney Disease in which the Polycystic Liver Volume Was Reduced by Rigorous Blood Pressure Control.

Polycystic liver disease (PLD) is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). However, current treatments for PLD are only supportive. We experienced a case of enlarged kidneys and liver in a 53-year-old Japanese man with ADPKD who was on hemodialysis. He underwent renal transcatheter arterial embolization (TAE) for enlarged kidneys. His blood pressure (BP) decreased after renal TAE, and his liver volume decreased from 5,259 mL to 4,647 mL (11.6% reduction) within 1 year after renal TAE. This case suggests that rigorous blood pressure control may be beneficial for ameliorating enlarged PLD.

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.

Renal Squamous Cell Carcinoma-related Polymyositis in a Patient with Autosomal Dominant Polycystic Kidney Disease.

A 74-year-old Japanese woman diagnosed with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our institute for the further examination of right-side groin pain developing in the past week. The patient was diagnosed with polymyositis (PM). Diagnostic imaging showed a mass lesion measuring 8 cm and a renal stone in the right kidney. Immediately following surgical resection of the right kidney, the patient's serum CK decreased to the normal range. A histopathological analysis showed well-differentiated squamous cell carcinoma. In conclusion, this case showed a close relationship between the occurrence of squamous cell carcinoma and the development of PM in an ADPKD patient.

Fabry Disease on Peritoneal Dialysis with Cardiac Involvement.

Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from a lack of alpha-galactosidase A (AGALA) activity in lysosomes. We herein report a patient with FD revealed by a renal biopsy who survived seven years after the introduction of peritoneal dialysis despite having severe heart failure due to left ventricular hypertrophy (LVH). FD was diagnosed based on a renal biopsy and biochemical analysis showing a low enzymatic activity of AGALA. A microscopic examination at the autopsy revealed marked hypertrophy and vacuolation of cardiac muscle cells. In our case, cardiac involvement determined the prognosis. Peritoneal dialysis is the modality of choice in the long-term management of dialysis patients with FD.

Abatacept Improves Intractable Protein-Losing Enteropathy Secondary to AA Amyloidosis in a Patient With Rheumatoid Arthritis.

A 71-year-old Japanese woman with a history of rheumatoid arthritis of 50 years' duration was admitted to our hospital with refractory diarrhea. Endoscopic biopsy revealed AA amyloid deposition in the large intestine. Although the patient had been prescribed 5 tumor necrosis factor inhibitors over the past 10 years, rheumatoid arthritis was poorly controlled, with a Disease Activity Score 28 using C-reactive protein score of 6.52 on admission. Treatment with tocilizumab (8 mg/kg every 2 weeks) was initiated, but this was ineffective. After 3 months, abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin) was initiated (750 mg/mo) and the patient's diarrhea began to improve. After 3 months of abatacept treatment, serum albumin, C-reactive protein, and serum amyloid A levels had all decreased to within normal ranges. After 3 years of abatacept treatment, a repeat biopsy of the large intestine revealed a marked improvement in amyloid deposition. Interleukin 6 is a key factor in AA amyloid formation, but this case suggests that T-cell activation increases the production of cytokines (including interleukin 6) via a mechanism involving cytotoxic T-lymphocyte-associated antigen 4, resulting in a second key factor of AA amyloid formation.

Outcome of renal cell carcinoma in patients on dialysis compared to non-dialysis patients.

PURPOSE: To investigate the impact of hemodialysis on survival in renal cell carcinoma (RCC) patients. METHODS: We studied 388 patients who underwent radical or partial nephrectomy for RCC at Toranomon Hospital from 2005 to 2013. Survival curves were drawn according to the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to assess the prognostic influence of hemodialysis on cancer-specific survival. RESULT: Of the 388 patients, 66 were on hemodialysis and 322 were not on dialysis. In the hemodialysis patients, incidental diagnosis of RCC was less frequent than in the non-dialysis patients. In addition, RCC was more likely to be multicentric (41% vs 1.2%), bilateral (14% vs 0.6%), and papillary (18% vs 7%) in hemodialysis patients. Moreover, tumors were smaller, the stage was lower, and the Fuhrman nuclear grade was higher in the patients on hemodialysis. The 5-year cancer-specific survival rate was 82.8% for hemodialysis patients and 93.5% for nondialysis patients. Multivariate analysis indicated that hemodialysis, stage, and Fuhrman nuclear grade were independent prognostic factors for RCC. CONCLUSIONS: This study suggested that hemodialysis was an independent prognostic factor for cancer-specific survival in RCC patients, along with the tumor stage and Fuhrman nuclear grade.

Rapidly progressive glomerulonephritis caused by tegafur/gimeracil/oteracil resulted in diabetes nephropathy, in a patient with minor risk of diabetes nephropathy: a case report.

A 79-year-old Japanese male with a history of type 2 diabetes mellitus (T2DM) for 16 years was admitted to evaluate possible renal disease. The T2DM was well controlled in this patient using nutrition therapy without the need for any diabetes medication, and both diabetes retinopathy and proteinuria were negative. At the age of 78 advanced colorectal cancer (stage IIIa) was diagnosed and laparoscopic-assisted colectomy was performed. Following this procedure, the patient began treatment with tegafur/gimeracil/oteracil (S-1), 80 mg twice daily for 28 days of 42-day cycle. The patient received S-1 for 6 months, during which time, serum albumin decreased from 3.0 g/dL to 1.1 g/dL, urinary protein increased from negative to 3.0 g/day, and serum creatinine increased from 0.9 mg/dL to 2.1 mg/dL. Treatment with S-1 was discontinued, and furosemide 180 mg and prednisolone 30 mg treatment was initiated; however, serum creatinine levels continued to increase to 7.2 mg/dL and proteinuria continued to increase reaching a nephrotic range. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity was decreased to 27.0%. Renal biopsy showed Kimmelstiel-Wilson nodules, while immunofluorescence intensity of IgG subclass was IgG1 dominant, which was not compatible with diabetic nephropathy (DN). Plasma exchange was not affected. However, hemodialysis was initiated.The results of this investigation suggest that when S-1 monotherapy is performed in the case with DN, rapidly progressive glomerulonephritis (RPGN) may develop due to a condition similar to thrombotic microangiopathy, even in patients with a minor risk factor of DN.

Characteristic Renal Histology of a 81-Year-Old Patient with a 30-Year History of Diabetes Mellitus: A Case Report.

A renal histology of an 81-year-old man with a 30-year history of diabetes mellitus (DM), as well as diabetic retinopathy and neuropathy, was examined. The patient's blood pressure was controlled within the normal range (less than 140/75 mmHg) using antihypertensive agents including angiotensin receptor blocker. Edematous management was achieved by a strict salt diet (less than 6 g/per day). However, this patient's glycemic control was poor with HbA1c 8-10%. Serum creatinine was 0.87 mg/dL and estimated globular filtration rate (eGFR) was 64 ml/min/1.73m2. Urinary protein excretion was 1.5 g/day. This patient's renal biopsy showed linear staining for IgG along the GBM by immunofluorescence microscopy, but light microscopy showed almost intact glomeruli, and the GBM was not thickened as revealed by electron microscopy with a width of 288-368 nm (< 430 nm). While arteriolar hyalinosis was severe, and polar vasculosis was observed around the glomerular vascular pole. This case indicates that long-standing hyperglycemia may induce polar vasculosis by the mechanism of angiogenesis, but diabetic glomerulopathy can become minor change, only when hypertension and edematous management could be controlled strictly.

Corticosteroid reduction by addition of cetirizine and montelukast in biopsy-proven minimal-change nephrotic syndrome concomitant with allergic disorders.

Recent reports suggest helper T-cell abnormalities in minimal-change nephrotic syndrome (MCNS), which often complicate allergic disorders that show a similar helper T-cell profile with Th2/Th17 predominance. However, the effect of anti-allergy therapy on MCNS remains unknown. This retrospective study included 51 patients with biopsy-proven MCNS recruited between November 2012 and October 2015, with follow-up through November 2017. We analyzed relapse and temporal daily corticosteroid dose with and without co-administration of histamine H1 receptor antagonist, cetirizine, and cysteinyl-leukotriene receptor antagonist, montelukast, as well as between baseline and after follow-up. Thirteen patients were treated with cetirizine and montelukast in addition to conventional therapy, whereas 38 patients were treated by conventional therapy only, consisting of corticosteroids and immunosuppressants. To adjust for baseline clinical characteristics, a 1:1 propensity score-matched model was applied. The clinical characteristics of the two groups after matching were similar at baseline. The treatment group showed a significant reduction in the lowest daily dose of oral prednisolone throughout the entire treatment course after the study compared to that of baseline (p < 0.025), which was not observed in the control group (p = 0.37), and showed significantly higher percentage of patients establishing corticosteroid-free state for the first time throughout the entire treatment course by addition of cetirizine and montelukast compared to the control group (p < 0.025). The study shows, for the first time, the steroid sparing effect of cetirizine and montelukast in addition to conventional treatment in MCNS patients with concomitant allergies.

Regression of renal amyloid deposits by VAD therapy plus autologous stem cell transplantation in a patient with primary AL amyloidosis.

We report a 58-year-old Japanese woman who presented with nephrotic syndrome. Steroid therapy and cyclosporine A administration were initiated, but hematological remission and renal response were not achieved. Renal biopsy revealed amyloid deposits in the mesangial region and the small arteries. Proteomic analysis based on laser microdissection and mass spectrometry showed that the amyloid deposits were composed of the constant region of the lambda light chain. She received vincristine, adriamycin, and dexamethasone therapy followed by high-dose melphalan and autologous stem cell transplantation, resulting in hematological complete remission and renal response with negative urinary Bence-Jones protein and proteinuria. Renal biopsy was performed four times during follow-up, demonstrating that amyloid deposits decreased gradually, while glomeruli showing global sclerosis increased from 3 to 62%. This case suggests that glomerular amyloid deposits can be cleared via tissue remodeling, if stem cells producing amyloid precursors are completely replaced by unrelated cells after stem cell transplantation.

PKD1-associated autosomal dominant polycystic kidney disease with glomerular cysts presenting with nephrotic syndrome caused by focal segmental glomerulosclerosis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) may manifest non-nephrotic range proteinuria, but is rarely complicated with nephrotic syndrome. Limited number of reports describe the histology of ADPKD with nephrotic syndrome in detail. CASE PRESENTATION: We encountered a 23-year-old man with polycystic kidney disease (PKD) with small kidney volume and nephrotic syndrome, which eventually progressed to end-stage renal disease. Renal histology showed typical focal segmental glomerulosclerosis and remarkable glomerular cyst formation, but did not reveal tubular cysts. PKD1 mutation was detected in him and his father, who also had PKD with small kidney volume. CONCLUSIONS: In contrast to tubular cysts which develop along ADPKD progression, glomerular cysts may likely be associated with ADPKD with slower volume progression manifesting small kidney volume. Although previous investigations report that ADPKD with smaller kidney volume is attributed to slower decline in renal function, coexistence of nephrotic-range proteinuria implies complication of other glomerular diseases and needs histological evaluation since it may lead to poor renal outcome.

Renal-Limited Thrombotic Microangiopathy due to Bevacizumab Therapy for Metastatic Colorectal Cancer: A Case Report.

An 88-year-old Japanese man received bevacizumab for colorectal cancer with liver and peritoneal metastasis, during which nephrotic range proteinuria occurred (7.66 g/day). Renal biopsy showed endothelial damage with subendothelial swelling and a double contour of the glomerular basement membrane, which indicated a diagnosis of thrombotic microangiopathy (TMA). After bevacizumab was stopped, proteinuria decreased to 1 g/day. During the clinical course, this patient had no extrarenal manifestations. This case suggests that renal injury induced by bevacizumab is characterized by nephrotic range proteinuria and histological TMA, and is a renal-limited condition that differs from systemic TMA related to thrombotic thrombocytopenic purpura.

An Orofaciodigital Syndrome 1 Patient and Her Mother Carry the Same OFD1 Mutation but Have Different X Chromosome Inactivation Patterns.

Orofaciodigital syndrome 1 (OFD-1) is a rare, X-linked, dominantly inherited disorder caused by an OFD1 mutation that can cause polycystic kidneys. A 37-year-old woman on hemodialysis therapy was admitted to our hospital for trans-catheter arterial embolization therapy for enlarged polycystic kidneys. Lobulated tongue and brachydactyly were noticed, prompting an OFD1 sequencing analysis. Sequencing revealed a causal four-base-pair deletion in exon 13, both in the patient and in her mother, whose renal function had been retained. The peripheral leukocyte X chromosome inactivation pattern was skewed in the patient but not in her mother, suggesting some role in their phenotypic difference.

Significance of urinary albumin excretion in patients with cast nephropathy
.

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.

Arteriovenous fistula-related renal bleeding 5 days after percutaneous renal biopsy.

A 32-year-old Japanese woman was admitted to our hospital for evaluation of microscopic hematuria with a positive family history. Percutaneous renal biopsy was performed under real-time ultrasound guidance using a 16-gauge automated needle and three specimens were obtained. She had no risk factors for hemorrhage. However, macroscopic hematuria developed from 5 days after biopsy and persisted for 4 days. Her Hb decreased markedly from 15.0 to 8.1 g/dL. Enhanced computed tomography revealed urinary tract hematoma, while the early arterial phase showed inflow of contrast medium into the left renal vein from a pseudoaneurysm on a branch left renal artery. Renal transcatheter arterial embolization was performed using platinum microcoils and the arteriovenous fistula was occluded. The patient did not require blood transfusion. Severe renal bleeding that causes urinary tract hematoma usually occurs within 24 h after renal biopsy, but the possibility of late-onset renal bleeding should be kept in mind.

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.

Long-term outcome of biopsy-proven cholesterol crystal embolism.

BACKGROUND: Cholesterol crystal embolism (CCE) causes renal damage, and there is an extremely high risk of end-stage renal disease. However, the time course of CCE-related renal deterioration varies and little is known about the subsequent risk of dialysis among patients with biopsy-proven CCE. METHODS: We performed a retrospective cohort study of 38 Japanese patients in whom a histological diagnosis of CCE was made from September 1992 to July 2005. Competing risk regression analysis was used to investigate the association between declining renal function ( ≥ 1.5 elevation of serum creatinine within 26 weeks after CCE) or its subtypes (acute [ < 1 week after CCE], subacute [1 to < 6 weeks], and chronic [6 to < 26 weeks]) and the risk of dialysis, with adjustment for age, baseline serum creatinine, and the precipitating event (iatrogenic or spontaneous). RESULTS: During a median follow-up period of 25.9 weeks, 14 patients (35.9%) started dialysis. Multivariable analysis showed that patients with declining renal function had a higher risk of commencing dialysis than those without declining function (subdistribution hazard ratio [SHR] 9.47; 95% confidence interval [CI] 1.34-66.8). Patients with different renal presentations had a similarly increased risk of commencing dialysis, with the risk being significantly higher for the subacute and chronic patterns of declining renal function (adjusted SHR [95% CI] for acute, subacute, and chronic declining renal function[vs. no decline]: 7.36 [0.85-63.6], 11.9 [1.36-101], and 10.7 [1.49-77.0], respectively). CONCLUSION: Declining renal function after CCE, even later than 6 weeks, was significantly associated with the subsequent risk of dialysis.