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.

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.

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.

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.

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.

Bone histomorphometric and immunohistological analysis for hyperostosis in a patient with SAPHO syndrome: A case report.

A 56-year-old Japanese woman with a history of palmoplantar pustulosis was admitted for examination due to left femur pain. Radiography and computed tomography showed thickening of the bone on the outer portion of the left femur. Bone scintigraphy of the left femur showed intense radioactive uptake. Consequently, the patient was diagnosed with SAPHO syndrome. Bone histomorphometric analysis of the left femur showed cancellous bone with thickened cortical bone. Whilst normal bone shows cancellous bone with double labeling (normal turn over), and cortical bone with no labeling (low turn over, adynamic state), this case presented with both cancellous and cortical bone with marked double labeling (indicating high turn over), abundant osteoid and woven bone. Immunohistological analysis showed that cells lining the bone surface consisted of osteoblasts and were positive for alkaline phosphatase (ALP). Few to little of these cells were positive for tartrate-resistant acid phosphatase (TRAP)-5B, cathepsin K and matrix metallopeptidase 9 (MMP-9). These results indicate that, in this case study, excessive production of osteoblasts contributed to hyperostosis of the left femur, with abundant osteoid and woven bone. This type of bone formation in SAPHO syndrome is not lamellar bone seen in normal bone, but rather fragile and mechanically weak bone, resulting in bone pain. Doxycycline may be a therapeutic option for bone pain in this patient.

Association between chronic kidney disease and incident diagnosis of dementia in England: a cohort study in Clinical Practice Research Datalink.

OBJECTIVES: To investigate the association between chronic kidney disease (CKD) and dementia diagnosis in a real-world primary care setting in England. DESIGN: Matched cohort study. SETTINGS: English primary care in the Clinical Practice Research Datalink. PARTICIPANTS: People aged ≥18 years with predialysis CKD (stages 3-5, defined as two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 for 3 months) from 2004 to 2014, and people without known CKD who were matched on age, sex, general practice and calendar time in a 1:1 ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: First-ever diagnosis of dementia recorded by GPs. We also examined all-cause death as a secondary outcome to discuss potential competing risk of mortality in the association between CKD and dementia diagnosis. RESULTS: In a matched cohort of 242 349 pairs with and without CKD (mean age 75.4±9.7 years, 39.3% male), the crude incidence rate of dementia diagnosis was 11.4/1000 and 9.4/1000 person-years, respectively. There was an association between CKD status and incident dementia diagnosis in the first 6 months of the follow-up (adjusted rate ratio (aRR) 1.58, 95% CI 1.44 to 1.74), which attenuated after 6 months (aRR 1.12, 95% CI 1.08 to 1.16). Among patients with CKD, there was no evidence of association between CKD stage and incident dementia diagnosis; compared with stage 3a, aRR (95% CI) was 1.04 (0.91 to 1.18) for stage 3b and 0.94 (0.74 to 1.20) for stages 4 or 5 in the first 6 months, and 0.97 (0.92 to 1.01) and 0.89 (0.80 to 0.98) thereafter. We found a strong association between worsening CKD stage and all-cause mortality. CONCLUSION: We identified a co-occurrence of detection of CKD and dementia in real-world clinical practice and a strong competing risk of mortality in the association between CKD stage and dementia, while a weak association between CKD status and dementia was suggested in the long term.

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.

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.

Candida albicans and Staphylococcus lugdunensis superinfection of liver cysts in a patient with autosomal dominant polycystic kidney disease under prednisolone treatment.

We report a case of superinfection of liver cysts caused by Candida albicans and Staphylococcus lugdunensis in a patient with autosomal dominant polycystic kidney disease. A 69-year-old man with chief complaints of headache and blurred vision was admitted to the former institution for the evaluation of suspected temporal arteritis. He was prescribed oral prednisolone (55 mg/day) as a preemptive treatment; however, he became febrile and presented with bilateral flank pain during prednisolone tapering. Blood culture revealed fungemia as a result of Candida famata infection; thus, micafungin treatment was started. Thereafter, recrudescence of the C-reactive protein level ensued. Then a cyst infection as visualized on magnetic resonance imaging led to cyst aspiration sclerotherapy. Cyst aspirate culture revealed the presence of C. albicans in one of the cysts and S. lugdunensis in two of the cysts. The patient was clinically stabilized with an additional 3 weeks of antibiotic and antifungal drug administration.

Denosumab for dialysis patients with osteoporosis: A cohort study.

Evidence for the efficacy of denosumab in HD patients is limited. Accordingly, here we report a study on the safety and efficacy of denosumab in these patients. We prospectively followed 324 patients (121 HD and 203 non-HD patients) receiving denosumab between June 2013 and May 2018, assessing changes in bone mineral density (BMD) and bone metabolic markers, and noting side-effects. Annual changes in BMD at the lumbar spine in HD and non-HD patients from baseline were, respectively, 6.7 ± 11.1% and 7.5 ± 10.2% (p = 0.60), those at the femoral neck were 4.3 ± 7.9% and 3.1 ± 9.5% (p = 0.32), and those at the distal radius were -0.5 ± 6.4% and 0.2 ± 13.0% (p = 0.66). The prevalence of hypocalcemia (<8.5 mg/dL) was significantly higher in HD than in non-HD patients (35.6% vs 5.4%, p < 0.001). The median elapsed time between the first injection of denosumab and the occurrence of hypocalcemia was 7 days in HD patients. The decrease of serum calcium was greater in patients with higher TRACP5b, corticosteroid use, and those without CaCO3 supplementation. Our study suggests that denosumab was equally as effective in HD as non-HD patients. However, careful hypocalcemia monitoring, for at least 4 weeks, is recommended for HD patients.

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.

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.

Significant polar vasculosis in a patient with a 30-year history of type 2 diabetes.

SUMMARY: We report the renal histology of a 66-year-old man with hypertension, cardiovascular disease, and a 30-year history of type 2 diabetes mellitus with proliferative diabetic retinopathy, diabetic neuropathy, and diabetic foot status post toe amputation. Urinary protein excretion was 1.4 g/gCr, serum creatinine level 0.86 mg/dL, estimated glomerular filtration rate 69 mL/min/1.73 m2, and HbA1c 13-15%, despite using insulin. Light microscopy showed global glomerulosclerosis in 37% of the glomeruli, but the remaining glomeruli were intact. Significant polar vasculosis was present, while arteriolar sclerosis was mild. Electron microscopy revealed a thickened glomerular basement membrane, which is compatible with the early stage of diabetic glomerulopathy. The presented case was unique because glomerular changes seen typically in diabetes were not seen in the patient, despite the long-standing history of diabetes and diabetic comorbidities, while prominent polar vasculosis was found. Polar vascular formation helps preserve the glomeruli by allowing hyperosmotic blood bypass the glomeruli; this decreases intraglomerular pressure and minimizes glomerular endothelial damage. LEARNING POINTS: A 66-year-old man with a 30-year history of type 2 diabetes mellitus with poor glycemic control underwent renal biopsy, which showed scarce glomerular changes typically seen in diabetic kidney disease and instead revealed significant polar vasculosis. Past studies demonstrated that the increased small vessels around the vascular hilus in diabetic patients originated from the afferent arterioles and drained into the peritubular capillaries. Polar vascular formation may preserve glomerular function by allowing the blood flow to bypass the glomeruli and decreasing the intraglomerular pressure, which minimizes endothelial damage of the glomerular tufts.

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.

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.

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.