tacrolimus and Glomerulonephritis--Membranoproliferative

Kimura's disease (KD) with renal involvement is a rare disease. Optimal treatments are still not well established. It is necessary to analyze clinicopathological features, treatment responses, and prognosis for improving KD diagnosis and treatment.. Clinicopathological data, treatment responses, and prognosis were collected and analyzed retrospectively.. The patients consisted of 27 males and 2 females, with an average age of 35.5 ± 15.1 (13 - 61) years. 27 exhibited proteinuria ranging from 0.730 to 14.1 g/24 h (5.98 ± 3.40 g/24 h). Hypertension, renal insufficiency (serum creatinine (Scr) > 1.24 mg/dL), and microhematuria occurred in 4 (13.8%), 11 (37.9%), and 13 (44.8%) cases, respectively. Light microscopy (LM) identified mesangium proliferation, minimal change, focal and segmental glomerulosclerosis (FSGS), membranous glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), and acute tubular necrosis in 14, 8, 3, 2, 1, and 1 cases, respectively. All were treated with Tripterygium wilfordii (TW), prednisone, leflunomide (LEF), tacrolimus (FK506), myophenolate mofetil (MMF), or renin-angiotensin system blockers (RASI). 26 patients were followed up for 1.60 - 108.7 months (39.6 ± 28.7). After treatments, urinary red blood cells (RBC) decreased in all. The amount of 24-hour urinary protein (24-hUPE) decreased in 24 patients. 22 reached complete remission (CR), 4 partial remissions (PR). The patients who did not relapse were younger than those who relapsed.. KD with renal involvement occurs predominantly among 35 - 50 year old Chinese patients with male predilection. The most common features are proteinuria, hypertension, micro hematuria with minimal change, and mesangial proliferative glomerulonephritis. Most were responsive to treatment, but could relapse. Gender, age, and hypertension are associated with KD recurrence. The prognosis is good mostly.

Topics: Adolescent; Adult; Angiolymphoid Hyperplasia with Eosinophilia; Anti-Inflammatory Agents; China; Female; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Hypertension; Immunosuppressive Agents; Isoxazoles; Leflunomide; Male; Middle Aged; Mycophenolic Acid; Phytotherapy; Plant Preparations; Prednisone; Prognosis; Proteinuria; Recurrence; Renal Insufficiency; Retrospective Studies; Tacrolimus; Tripterygium; Young Adult

To investigate the clinical characteristics and histopathological features of kidney disease in elderly patients.. We retrospectively analyzed the results of 4,185 consecutive renal biopsies, and 288 patients aged >60 years at the Second Hospital of Jilin University from January 1998 to December 2013 were finally included. All patients had been clinically and histologically diagnosed with kidney disease.. Nephrotic syndrome was the main clinical indication for biopsy. Twenty-four patients (8.33 %) experienced a minor complication related to their biopsy procedure. Among patients diagnosed as primary glomerulonephritis (GN), membranous nephropathy (MN) was the most frequent subclassification (24.7 %), followed by mesangioproliferative glomerulonephritis (MsPGN, 11.1 %) and IgA nephropathy (IgAN, 8.0 %). Amyloidosis (8.7 %) was the most common secondary GN, followed by antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune GN (5.2 %) and diabetic nephropathy (DN, 3.8 %). Based on renal biopsies results, 143/288 patients received immunosuppressive therapy and showed an overall remission rate (complete plus partial remissions) of 74.1 %. Among 71 MN patients, 29 patients received steroids plus cyclophosphamide and showed a remission rate of 79.3 %, while 42 patients received steroids and tacrolimus and showed a remission rate of 90.5 %. Among 25 patients with amyloidosis, 22 cases received melphalan plus dexamethasone and showed a remission rate of 40.9 %, while three patients received vincristine, adriamycin, and dexamethasone and showed a remission rate of 66.7 %.. Making an accurate pathologic diagnosis by renal biopsy is crucial for selecting the proper treatment for elderly patients with kidney disease.

Topics: Aged; Aged, 80 and over; Amyloidosis; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antineoplastic Agents, Alkylating; Autoimmune Diseases; Biopsy; Cyclophosphamide; Dexamethasone; Diabetic Nephropathies; Female; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Retrospective Studies; Tacrolimus; Treatment Outcome

Standard treatment for class III, IV, and V lupus nephritis (LN) is a combination of oral corticosteroids and mycophenolate mofetil (MMF). There is an estimated failure rate of 16%. Several small studies have looked at the use of tacrolimus in class III, IV, and V LN, both as induction treatment and as maintenance in patients refractory to other treatments. The majority of these studies were conducted in Asian patients. We discuss a cohort of eight female patients of various ethnicities with biopsy proven LN. All patients were evaluated retrospectively. Six were started on tacrolimus after failing to respond to MMF and corticosteroids, and one was started on tacrolimus alone because treatment options were limited by pregnancy. Five were Caucasian, one African American, one Hispanic, and one Vietnamese. Mean tacrolimus dose was 3.3mg daily (range 2-5 mg) titrated to a mean level of 3-6 ng/dl (range 3-6.6 ng/dl) for a mean of duration of 16 months (range 2-54 months). Six patients experienced complete remission (proteinuria <0.33 g/day), and two patients had a partial remission (minimum of 50% reduction in baseline proteinuria). Albumin increased an average of 32%. Average C3/C4 levels were 64/15 mg/dL, respectively, prior to treatment, and 95/25 mg/dL following treatment. No treatment-limiting adverse effects were reported. Our case series supports the growing body of evidence that tacrolimus is an effective therapy in LN patients with refractory proteinuria. Further studies are required to establish the long-term safety and efficacy of tacrolimus.

Topics: Adult; Female; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Lupus Nephritis; Proteinuria; Retrospective Studies; Tacrolimus; Young Adult

Acute antibody mediated rejection (AMR) is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA) and cyclosporine A (CsA). Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr.) to 210 μmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN) with focal crescent formation, diffuse immune complex deposition and peritubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab). AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 μmol/L.

Topics: Acute Disease; Antibodies; Antibodies, Monoclonal, Murine-Derived; Drug Therapy, Combination; Glomerulonephritis, Membranoproliferative; Graft Rejection; Histocompatibility Testing; HLA Antigens; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Nephrotic Syndrome; Plasmapheresis; Rituximab; Tacrolimus; Time Factors; Treatment Outcome

In a proportion of adults with steroid-resistant nephrotic syndrome (SRNS), intravenous cyclophosphamide therapy fails. Tacrolimus may be a promising alternative to cyclophosphamide for such patients.. Prospective observational study.. 19 adults with SRNS (6 with minimal change nephropathy, 8 with focal segmental glomerulosclerosis [FSGS], and 5 with mesangioproliferative glomerulonephritis) that did not respond to intravenous cyclophosphamide therapy were studied from January 2003 to September 2006. Oral tacrolimus was administered (target trough levels, 5 to 10 ng/mL) for 24 weeks, then reduced doses were given (target trough level, 3 to 6 ng/mL) for another 24 weeks.. Histopathologic types: minimal change nephropathy (n = 6), FSGS (n = 8), and mesangioproliferative glomerulonephritis (n = 5).. outcome variables included complete remission (decrease in daily proteinuria to protein < or = 0.3 g/d), partial remission (decrease in daily proteinuria to protein < 3.5 g/d but > 0.3 g/d), relapse (increase in daily proteinuria to protein > or = 3.5 g/d in patients who had partial or complete remission), change in kidney function, and tacrolimus dosing and serum levels.. 17 patients completed at least 24 weeks of tacrolimus therapy. Complete remission was achieved in 11 patients (64.7%), and partial remission was achieved in 3 (17.6%). Complete or partial remission was achieved in 5 of 5 patients with minimal change nephropathy, 4 of 7 patients with FSGS, and 5 of 5 patients with mesangioproliferative glomerulonephritis. Primary resistance to tacrolimus was seen in 3 patients (17.6%), all with FSGS. Mean times to achieve partial and complete remission were 5.6 +/- 1.4 and 8.0 +/- 5.1 weeks, respectively. In patients who achieved complete or partial remission, 35.7% experienced relapse during follow-up (mean, 37.6 +/- 13.4 months). Two patients had doubling of serum creatinine levels, both with FSGS.. Observational study.. Tacrolimus rapidly and effectively induced remission of SRNS in Chinese adults with disease refractory to treatment with intravenous cyclophosphamide. Treatment may be less effective in patients with FSGS.

Topics: Administration, Oral; Adolescent; Adult; China; Creatinine; Cyclophosphamide; Drug Resistance; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulonephritis, Membranoproliferative; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Injections, Intravenous; Male; Nephrosis, Lipoid; Nephrotic Syndrome; Prospective Studies; Retrospective Studies; Steroids; Tacrolimus; Treatment Outcome; Young Adult

Herein, we describe the case of an 8-year-old boy who presented with a nephritic nephrotic syndrome. His laboratory investigation was significant for a persistently low serum complement 3 level. A renal biopsy was performed, based on which, he was diagnosed with dense deposit disease/membranoproliferative glomerulonephritis type II (DDD/MPGN II). He was treated with alternate-day oral corticosteroids, angiotensin-converting enzyme (ACE) inhibitors and tacrolimus. Factor H mutational analysis showed the Y402H and I62V allele polymorphisms. The purpose of our report is to discuss the association of the H402 allele variant of factor H with the DDD/MPGN II phenotype and its possible therapeutic implications.

Topics: Adrenal Cortex Hormones; Alleles; Angiotensin-Converting Enzyme Inhibitors; Child; Chromosome Mapping; Complement Factor H; Drug Therapy, Combination; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Male; Polymorphism, Genetic; Tacrolimus

Membranoproliferative glomerulonephritis, albeit uncommon, is associated with considerable morbidity and mortality in children. Corticosteroids are the mainstay of therapy for severe disease, although data supporting their use are limited. We report our experience in treating two children with nephrotic-nephritic syndrome from idiopathic membranoproliferative glomerulonephritis. Both children experienced a suboptimal response to prolonged courses of steroids and were started on tacrolimus as a steroid-sparing agent. Rapid and complete remission was achieved in both children after initiation of tacrolimus. The purpose of our report is to increase awareness of health care professionals to the potential benefits of this agent in inducing remission in children with severe membranoproliferative glomerulonephritis.

Topics: Child; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Male; Nephrotic Syndrome; Tacrolimus; Treatment Outcome

To evaluate the efficacy of FK506 in the treatment of children with nephrotic syndrome of different underlying pathology.. 12 patients were treated with FK506 with a dosage of 0.1 - 0.15 mg/kg/d while corticosteroid dose was tapered stepwise. This therapeutic course lasted 3 - 6 months during which the plasma concentration ofFK506 was monitored.. 12 children with different pathological types nephrotic syndrome were treated with FK506, including 4 cases of MCN, 6 cases of MsPGN, and 1 case of MPGN and 1 case of FSGS. After 2-month duration, 8 patients got complete remission including 4 cases of MCN and 4 cases of MsPGN and 3 children including 1 case of MsPGN, 1 case of MPGN, and 1 case of FSGS got partial remission. Only 1 child with MsPGN was considered to be a treatment failure. The overall response rate was 91.67% with the plasma concentration of FK506 maintained at 5 approximately 12 ng/ml, and the response time was 10 - 38 days. After 1-month duration, all patients except one experienced a reduction in proteinuria to normal levels or a partial response (50% reduction in protein excretion), significant increase in serum albumin, decrease in serum cholesterol and triglyceride and disappearance of edema. 2 months later, in 11 patients, blood biochemical values had returned to normal levels. The drug was generally well-tolerated. 3 patients had anorexia, nausea, vomiting. 2 patients experienced transient elevated serum creatinine which was reversible after the adjustment of dosage. 3 patients had minor changes in urine NAG. Only 2 of all patients relapsed.. FK506 is one of the effective immunosuppressants. In this study, FK506 in combination with a small doses of steroid while decreasing FK506 dosage plays a role in consolidating the curative effect and preventing relapse. In conclusion, FK506 may be effective in the treatment of nephrotic syndrome.

Topics: Adolescent; Adrenal Cortex Hormones; Child; Child, Preschool; Female; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney; Male; Nephrotic Syndrome; Tacrolimus