Relapse during and after regular single-dose rituximab treatment in adult patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. METHODS: This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500 mg) intravenously every 6 months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. RESULTS: The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1 year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3 years and 7 months. The 1 and 2 year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2 year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. CONCLUSION: All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2 years after discontinuing rituximab treatment.

Renal injury associated with MYH9 disorder with 5773delG mutation: A case report.

A 35-year-old man with persistent urine abnormalities and renal dysfunction was referred to our hospital. May-Hegglin anomaly was suspected, and a renal biopsy showed focal segmental glomerulosclerosis (FSGS) with IgA deposition. Electron microscopy revealed foot process effacements and intense bleb-like morphological changes in podocytes. Nonmuscle myosin heavy chain IIA (NMMHCIIA) staining of granulocytes revealed a localized, type II pattern, and genomic DNA sequencing of MYH9 exon 40 revealed MYH9 5773delG mutation (c.5773delG [p.(Asp1925Thrfs*23)]). Podocytes were significantly stained by an antibody specific for NMMHC-IIA abnormalities associated with this mutation. Colocalization observation of vimentin and NMMHC-IIA demonstrated a diminished form of NMMHC-IIA in podocytes. Taking these observations into account, it was determined that the present case was likely associated with MYH9 disorder. Treatment was started with olmesartan, followed by methylprednisolone pulse therapy 3 times bi-monthly. Finally, the patient began hemodialysis 18 months later. This is the first known report of renal phenotype expression associated with this MYH9 mutation. FSGS can occur in association with MYH9 mutations at the 3' regions, such as exon 40. Abnormal expression or metabolism of NMMHC-IIA in podocytes might be related to the formation of FSGS lesions due to this MYH9 mutation.

Association of Familial Fanconi Syndrome with a Novel GATM Variant.

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.

Chemoprophylaxis against Pneumocystis jirovecii pneumonia in Japanese patients with ANCA-associated vasculitis: An observational study.

OBJECTIVES: This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. RESULTS: Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). CONCLUSIONS: The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.

Methylglyoxal as a prognostic factor in patients with chronic kidney disease.

AIM: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. METHODS: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model. RESULTS: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome. CONCLUSION: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.

Liddle's-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: the first case report.

BACKGROUND: Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) ß or γ subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically improves the disease condition. Although elderly patients having these characteristics were considered to have Liddle's syndrome or Liddle's-like syndrome, no previous report has indicated that Liddle's-like syndrome could be caused by nephrotic syndrome of primary glomerular disease, which is characterized by urinary excretion of > 3 g of protein/day plus edema and hypoalbuminemia, or has explained how the activity function of ENaC could be affected in the setting of high proteinuria. CASE PRESENTATION: A 65-year-old Japanese man presented with nephrotic syndrome. He had no remarkable family history, but had a medical history of hypertension and hyperlipidemia. On admission, hypertension, spironolactone-resistant hypokalemia (2.43 mEq/l), hyporeninemic hypoaldosteronism, and metabolic alkalosis, which suggested Liddle's syndrome, were observed. Treatment with triamterene together with a steroid for nephrotic syndrome resulted in rapid and remarkable effective on improvements of hypertension, hypokalemia, and edema of the lower extremities. Renal biopsy revealed membranous nephropathy (MN) as the cause of nephrotic syndrome, and advanced gastric cancer was identified on screening examination for cancers that could be associated with the development of MN. After total gastrectomy, triamterene was not required and proteinuria decreased. A mutation in the ß or γ subunits of the ENaC gene was not identified. CONCLUSION: We reported for the first time a case of Liddle's-like syndrome associated with nephrotic syndrome secondary to MN. Aberrant activation of ENaC was suggested transient during the period of high proteinuria, and the activation was reversible with a decrease in proteinuria.

Effects of cyclophosphamide on the prognosis of Japanese patients with renal vasculitis associated with anti-neutrophil cytoplasmic antibody-positive microscopic polyangiitis.

BACKGROUND: The aim of this study was to determine the efficacy of cyclophosphamide (CY) on anti-neutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA) with renal involvement in Japanese patients. METHODS: Eighty-two patients with newly diagnosed ANCA-positive MPA were enrolled in this retrospective study. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY group) or CS alone or with other therapies (non-CY group). The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). RESULTS: The CY and non-CY groups included 29 and 53 patients, respectively. In the non-CY group, 31 patients were treated with CS alone, and 22 with a combination of CS and other therapeutics. The percentage of males and mean Birmingham vasculitis activity scores were higher in the CY group than those in the non-CY group, but other factors such as age, serum creatinine, serum albumin, or CRP at baseline were equivalent in the two groups. No differences were observed in remission rates using induction therapy for the two groups. However, the survival rate 5 years after induction therapy was lower in the CY group than in the non-CY group (0.50 vs. 0.73; P = 0.041), although the hazard ratio of CY for the primary outcome adjusted for all confounding factors was 1.321 [95 % confidence interval (CI), 0.662-2.637; P = 0.171]. CONCLUSIONS: CY may not have an additive effect on induction therapy with CS for Japanese patients with renal vasculitis associated with ANCA-positive MPA.

A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy.

BACKGROUND: The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). METHODS: Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. RESULTS: During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01-8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. CONCLUSIONS: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

Heavy chain deposition disease: an overview.

Heavy chain deposition disease (HCDD) is one of three entities of monoclonal immunoglobulin deposition disease, characterized histopathologically by the presence of nodular glomerulosclerosis and glomerular and tubular deposition of monoclonal heavy chains without associated light chains. Although HCDD is an extremely rare disease, >30 cases have been reported to date in the literature. Of these cases, only three cases have been reported in Japan. The majority of the patients presents with nephrotic syndrome, hematuria, and hypertension, and develop progressive renal failure with or without the complication of multiple myeloma. Some cases have been treated successfully using chemotherapy. Because of its rarity, a thorough understanding of HCDD is essential for both accurate diagnosis and adequate subsequent treatment.

Proliferative glomerulonephritis with monoclonal IgM deposits without Waldenström's macroglobulinemia: case report and review of the literature.

A 38-year-old man was presented with nephrotic syndrome associated with hematuria and mild hypocomplementemia. Renal biopsy revealed lobular mesangial proliferation, thickened capillary walls, and intraluminal protein thrombi. Immunofluorescence showed marked and mild depositions of immunoglobulin (Ig) M heavy chains and complement C3, respectively, in a peripheral lobular pattern. On light chain staining, only kappa (κ) light and IgM heavy chains showed a similar pattern. Electron microscopy showed fine granular electrondense deposits in subendothelial areas and numerous globular deposits (varying size and density) in glomerular capillary lumens. Serum levels of Ig κ, but not of free κ, light chains were significantly increased. Bone marrow aspiration revealed a normocellular marrow. Waldenström's macroglobulinemia and cryoglobulinemia were ruled out. Clinically, steroid therapy was ineffective and proteinuria persisted. This report demonstrates that glomerular deposition of monoclonal IgM-κ can produce membranoproliferative- like changes in the glomeruli. This condition may be recognized as proliferative glomerulonephritis with monoclonal IgM deposits similar to the recently recognized proliferative glomerulonephritis with monoclonal IgG deposits.

κ I light chain AL amyloidosis presenting with rapidly progressive renal and hepatic failure with unusual renal amyloid distribution.

A 65-year-old man suffering from generalized edema and jaundice was admitted to our hospital. Laboratory findings revealed marked renal dysfunction with heavy proteinuria as well as liver dysfunction with severe obstructive jaundice. On renal biopsy, the diagnosis of AL amyloidosis associated with κ I light chain was made. Interestingly, amyloid deposits were restricted to the glomeruli. Although hemodialysis was initiated, the patient died due to further deterioration of hepatic function. On autopsy, severe intrahepatic cholestasis was observed, and there was marked deposition of AL amyloid in the liver. Literature reviews showed that rapidly progressive renal failure is common in AL amyloidosis patients who presented with acute hepatic failure due to severe intrahepatic cholestasis. However, the detailed renal pathology in this condition has not been documented. The present case is very interesting because rapidly progressive renal and hepatic failure was simultaneously observed, and renal amyloid deposition was restricted to the glomeruli.

Pulmonary hypertension confirmed histologically five months prior to scleroderma renal crisis onset.

A 69-year-old man presented shortness of breath and acute renal failure. He had undergone pulmonary partial resection for lung cancer 5 months prior. On examination, severe hypertension, skin sclerosis of his forearms, and anticentromere antibody were observed. A renal biopsy specimen showed characteristic findings for scleroderma renal crisis, and a right heart catheterization revealed severe pulmonary arterial hypertension. Re-examination of the resected lung specimen revealed sclerodermatous vascular involvement was present.

Damage control surgery for grade IV blunt hepatic injury with multiple organ damage in a child: a case report.

BACKGROUND: Intra-abdominal hemorrhage caused by blunt hepatic injury is a major cause of morbidity and mortality in patients with abdominal trauma. Some of these patients require laparotomy, and rapid decision-making and life-saving surgery are essential. Damage control (DC) surgery is useful for treating children in critical situations. We performed this technique to treat an 8-year-old boy with grade IV blunt hepatic injury and multiple organ damage. This is the first report of the use of the ABTHERA Open Abdomen Negative Pressure Therapy System (KCI, now part of 3 M Company, San Antonio, TX, USA) for DC surgery to rescue a patient without neurological sequelae. CASE PRESENTATION: An 8-year-old boy was brought to the emergency department of our hospital after being run over by a motor vehicle. He had grade IV blunt hepatic injury, thyroid injury, and bilateral hemopneumothorax. Although he was hemodynamically stable, the patient's altered level of consciousness, the presence of a sign of peritoneal irritation, and suspicion of intestinal injury led us to perform exploratory laparotomy. As part of a DC strategy, we performed gauze packing to control hemorrhage from the liver and covered the abdomen with an ABTHERA Open Abdomen Negative Pressure Therapy System to improve the patient's general condition. Eighteen days after admission, the patient was diagnosed with a biliary fistula, which improved with percutaneous and external drainage. He had no neurological sequelae and was discharged 102 days after injury. CONCLUSION: The DC strategy was effective in children with severe blunt hepatic injury. We opted to perform DC surgery because children have less hemodynamic reserve than adults, and we believe that using this strategy before the appearance of trauma triad of death could save lives and improve outcomes. During conservative management, it is important to adopt a multistage, flexible approach to achieve a good outcome.

Orthogonal antibody testing for COVID-19 among healthcare workers in a non-epidemic place and time:Japan's Iwate Prefecture, May 18-31, 2020.

Of the 47 prefectures in Japan, Iwate had the fewest cases of coronavirus disease 2019 (COVID-19), with the first diagnosis officially confirmed on July 28, 2020. A baseline serological survey of COVID-19 antibodies is essential to accurately evaluate an epidemic outbreak. The primary purpose of this study was to determine pre-epidemic prevalence of COVID-19 antibodies among healthcare workers, using two laboratory-based quantitative tests. In addition, a point-of-care (POC) qualitative test, rapid, simple, and convenient for primary care clinics, was compared with the laboratory-based tests. All antibody tests were performed on serum from 1,000 healthcare workers (mean age, 40 ± 11 years) in Iwate Prefectural Central Hospital, May 29-31, 2020. A COVID-19 case was defined as showing positive results in both laboratory-based quantitative tests. None of 1,000 samples had positive results in both of the laboratory immunoassays. The POC test showed positive results in 33 of 1,000 samples (3.3%) (95% confidence interval:2.19-4.41), but no samples were simultaneously positive in both laboratory-based tests. In conclusion, COVID-19 cases were not serologically confirmed by a baseline control study of healthcare workers at our hospital in late May, 2020. Moreover, the POC qualitative test may offer no advantage in areas with very low prevalence of COVID-19, due to higher false-positive reactions compared with laboratory-based quantitative immunoassays.

First case report of monoclonal IgG3-heavy-chain glomerulonephritis with microtubular structures.

Our patient was a 69-year-old woman admitted to our hospital for heavy proteinuria and hematuria. A renal biopsy showed findings similar to those of membranoproliferative glomerulonephritis associated with nodular lesions, and immunofluorescence showed marked deposits of IgG, C1q, and C3 on the peripheral capillary walls. IgG3 alone was observed on IgG subclass staining with no κ or λ light chains, and Congo red staining was negative. These findings suggested IgG3-heavy-chain deposition disease (HCDD). However, we did not find a deletion of the first heavy-chain constant domain, which is commonly observed in HCDD. Electron microscopy showed randomly arranged subendothelial microtubular structures with diameters of 70-90 nm. Altogether, the diagnosis of HCDD could not be made, although monoclonal IgG3 deposits in glomeruli were observed. This is the first case report of monoclonal IgG3-heavy-chain glomerulonephritis with subendothelial-based, randomly arranged microtubular structures with diameters of 70-90 nm.

Tonsillectomy and steroid pulse (TSP) therapy for patients with IgA nephropathy: a nationwide survey of TSP therapy in Japan and an analysis of the predictive factors for resistance to TSP therapy.

BACKGROUND: Tonsillectomy and steroid pulse (TSP) therapy was proposed as a curative treatment for IgA nephropathy by Hotta et al. (Am J Kidney Dis 38:736-742, 2001) based on data that about 50% of patients achieved clinical remission (CR) of urinary abnormalities. MATERIALS AND METHODS: As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP therapy for patients with IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP therapy. RESULTS: A total of 2,746 patients received TSP therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of proteinuria (g/day; P = 0.02), total protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800-2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP therapy (6.9 +/- 6.8 versus 5.3 +/- 5.2 years; P = 0.02), amount of proteinuria (1.5 +/- 1.6 versus 0.8 +/- 0.8 g/day; P < 0.0001), serum creatinine (0.99 +/- 0.40 versus 0.87 +/- 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.'s prognostic score (37.4 +/- 17.8 versus 28.1 +/- 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP therapy depends on age at onset, amount of proteinuria, hematuria grade, and pathological grade, and a score predicting resistance to TSP therapy could be derived by the formula: [(-0.0330) x (age) + (0.4772) x log (amount of proteinuria) - (0.0273) x (hematuria grade: 0, 1, 2, and 3) + (0.7604) x (pathological grade: 1, 2, 3, and 4) - 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than -0.02 easily resist TSP therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76). CONCLUSION: TSP therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year after treatment. Predictive factors for resistance to TSP therapy are age at onset, amount of proteinuria, hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate IgA nephropathy easily achieve CR following TSP therapy, whereas patients with late-stage or severe disease are prone to TSP therapy resistance.

[Massive colonic bleeding and crescentic glomerulonephritis in an elderly man with Henoch-Schönlein purpura].

A 79-year-old man with an artificial anus constructed during surgical repair of colon perforation of unknown etiology in 1995 was admitted to our hospital for sudden appearance of purpura in the lower extremities. Two weeks before admission, he complained of flu-like symptoms and abdominal pain. He was diagnosed with Henoch-Schonlein purpura (HSP), which responded to treatment with 30 mg day oral prednisolone (PSL). Subsequently, however, rapid deterioration of renal function associated with severe hematuria and proteinuria was noted. Renal biopsy on hospitalization day 14 showed cellular crescent formation in more than half of the glomeruli with granular deposits of IgA, C3 and fibrinogen in the mesangium and on the capillary walls. PSL was tapered to 20 mg day from hospitalization day 14 because of a further decrease in purpura and a decrease in C-reactive protein. On hospitalization day 19, serum creatinine increased to 3.1 mg dL and a massive bloody stool was observed. Colonoscopy revealed extensive oozing from the colonic mucosa around the artificial anus. Since the bleeding was considered to result from HSP activity, methylprednisolone pulse therapy was applied, followed by increasing the dose of oral PSL to 30 mg/day. Co-administration of cyclophosphamide (25 mg day) from hospitalization day 39 led to improvement of renal dysfunction and a decrease in proteinuna at the outpatient clinic.

Distinct characteristics and outcomes in elderly-onset IgA vasculitis (Henoch-Schönlein purpura) with nephritis: Nationwide cohort study of data from the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: The clinical presentation and prognosis of adult and elderly patients with IgA vasculitis (Henoch-Schönlein purpura) accompanied by nephritis (IgAV-N) have not been investigated in detail. We therefore surveyed the features and outcomes of IgAV-N based on nationwide data derived from the Japan Renal Biopsy Registry (J-RBR). METHODS: This multi-center cohort study compared the clinicopathological parameters at diagnosis, initial therapies and outcomes between 106 adult (age 19-64 years) and 46 elderly (≥65 years) patients with IgAV-N who were registered in the J-RBR between 2007 and 2012. The primary end-points comprised a 50% increase in serum creatinine (sCr) values or end-stage kidney disease. Factors affecting a decrease in renal function were assessed using Cox proportional hazards models. RESULTS: Rates of hypertension, impaired renal function, hypoalbuminemia and crescentic glomerulonephritis were significantly higher among the elderly, than the adult patients. About 80% and 60% of the patients in both groups were respectively treated with corticosteroid and a renin-angiotensin system (RAS) blockade. Both groups had favorable renal survival rates for nine years (93.6% and 91.4% of the adult and elderly patients, respectively). Significantly more elderly than adult patients developed a 50% increase in sCr during a mean observation period of 3.9 years (21.7% vs. 4.7%, p = 0.012), and significantly fewer elderly, than adult patients achieved clinical remission (23.9% vs. 46.2%, p = 0.016). Multivariate analysis selected advanced age (≥65 years) and lower serum albumin values as independent prognostic factors for a decline in renal function, whereas steroid pulse therapy helped to preserve renal function. CONCLUSIONS: The renal prognosis of adult and elderly patients with IgAV-N was favorable when treated aggressively with corticosteroid and RAS blockade. However, the course of renal function should be carefully monitored in patients aged over 65 years and those with hypoalbuminemia.