Resolution Of Proteinuria Research Articles

7876 Complex Complications of Thionamide Therapy in One Patient: Methimazole-Induced Agranulocytosis and PTU-Induced ANCA-Vasculitis

Abstract Disclosure: E. Zweibach: None. A. Chang: None. Introduction: Thionamides, including methimazole and propylthiouracil (PTU), are essential for treating Graves' disease but can cause serious side effects such as agranulocytosis and ANCA-vasculitis. Although agranulocytosis itself is quite uncommon, the incidence of ANCA vasculitis is even more infrequent, making combination of conditions particularly exceptional. We present a unique case of a Graves' disease patient who suffered both complications: agranulocytosis due to methimazole and ANCA vasculitis from PTU, with successful resolution of both the clinical signs and laboratory findings following drug discontinuation. Case: 61-year-old female with a history of Graves' disease previously managed with methimazole but discontinued due to agranulocytosis, presented with lower extremity swelling, atrial fibrillation with RVR, and high output cardiac failure. Laboratory tests showed hyperthyroidism (TSH 0.008, Free T4 3.07), leading to a diagnosis of thyroid storm. Patient was started on PTU inpatient and discharged with this medication to home. Eight months later, the patient developed alarming signs including gross hematuria, oral ulcers, widespread muscle pain, found to have AKI with Cr of 2.79 and hospitalized for further eval. While hospitalized, the patient was found to have a range of complications including leukopenia with normal granulocyte count, anemia, AKI, proteinuria, and microscopic hematuria. Rheumatological evaluation showed +ANA and a high ANCA titer >1:1280, along with elevated levels of MPO and PR-3, and reduced complement levels. These symptoms and laboratory findings led to a diagnosis of ANCA vasculitis induced by PTU, resulting in the cessation of this medication. Following the discontinuation of PTU there was a notable improvement with normalization of serum Cr and resolution of proteinuria within 1.5 months. Concurrently, MPO and PR-3 levels began to decrease, and her hematological abnormalities resolved. During this period, her Free T4 levels gradually increased, leading to the administration of radioactive iodine for the treatment of her Graves' disease. Discussion: This case underscores the complexities in treating a patient with Graves' disease highlighting the unpredictable and severe side effects of antithyroid drugs like agranulocytosis and ANCA vasculitis. We report the first documented case of sequential thionamide-induced complications: agranulocytosis with methimazole, followed by ANCA vasculitis with propylthiouracil. Although both can arise from immune responses to these medications, they are distinct in their pathophysiology and are not associated with one another. The unpredictable nature of these side effects complicates prevention. Educating patients to promptly report any unusual symptoms and immediate medical intervention with drug discontinuation are key to managing these adverse reactions effectively. Presentation: 6/1/2024

Safety and efficacy of low-dose glucocorticoid regimen in the induction phase treatment of class 4, 5 lupus nephritis

Background Renal involvement in systemic lupus erythematosus is known as lupus nephritis (LN). LN presents with varied renal features. Class 4 and 5 LN are traditionally treated with prolonged standard high doses of prednisolone with various immunosuppressants such as cyclophosphamide and mycophenolate. These high doses of prednisolone are associated with numerous side effects. There is deficient data on the dose, duration of glucocorticoid therapy, and also paucity of data on comparison between the standard dose versus low-dose glucocorticoid therapy. Hence, this study can help in evaluating the use of low-dose glucocorticoids, its impact on renal outcome, and looking at side effects. Materials and methods It was a retrospective observational study conducted to look at the safety and efficacy of low-dose glucocorticoid regimen in induction phase treatment of class 4, 5 LN. Results On treatment, it was found that the resolution of microscopic hematuria, and improvement of low C4, and hypoalbuminemia were statistically significant in the low-dose steroid group. The resolution of proteinuria was seen in both groups and the resolution of renal failure was noted in both groups but was statistically significant in the standard dose group. Increased incidence of steroid-related complications was seen in the standard dose steroid group. Conclusions These findings possibly indicate that low-dose steroid therapy is good enough to treat LN with proteinuria, but a standard dose steroid is required in the presence of renal failure in LN, though increased incidence of steroid-related complications was seen in the standard dose steroid group.

One-third of patients with lupus nephritis classified as complete responders continue to accrue progressive renal damage despite resolution of proteinuria

ObjectiveTreatment response in lupus nephritis (LN) is defined based on proteinuria, yet protocol kidney biopsy studies have shown that patients with lupus can have active nephritis in the absence of...

The use of telmisartan in combination therapy in the management of nephrotic syndrome due to non‐immune‐mediated glomerulonephropathy in a young cat

AbstractAn 8‐month‐old male castrated domestic shorthair was referred with anorexia, polydipsia, lethargy and diarrhoea, which progressed to marked subcutaneous oedema. The cat had hypoalbuminaemia, hypercholesterolaemia, proteinuria and oedema; clinicopathological findings consistent with severe protein‐losing nephropathy and nephrotic syndrome. Histopathology of ultrasound‐guided percutaneous renal biopsies identified marked podocyte injury with associated focal segmental glomerulosclerosis, a condition rarely reported in cats. The cat fully recovered following medical management with prednisolone and telmisartan, with the resolution of proteinuria.

Preclinical Dose-Escalation Study of ZSJ-0228, a Polymeric Dexamethasone Prodrug, in the Treatment of Murine Lupus Nephritis.

Glucocorticoids (GCs) are widely used in the clinical management of lupus nephritis (LN). Their long-term use, however, is associated with the risk of significant systemic side effects. We have developed a poly(ethylene glycol) (PEG)-based dexamethasone (Dex) prodrug (i.e., ZSJ-0228) and in a previous study, demonstrated its potential therapeutic efficacy in mice with established LN, while avoiding systemic GC-associated toxicity. In the present study, we have employed a dose-escalation design to establish the optimal dose-response relationships for ZSJ-0228 in treating LN and further investigated the safety of ZSJ-0228 in lupus-prone NZB/W F1 mice with established nephritis. ZSJ-0228 was intravenously (i.v.) administered monthly at four levels: 0.5 (L1), 1.0 (L2), 3.0 (L3), and 8.0 (L4) mg/kg/day Dex equivalent. For controls, mice were treated with i.v. saline every 4 weeks. In addition, a group of mice received intraperitoneal injections (i.p.) of Dex every day or i.v. injections of Dex every four weeks. Treatment of mice with LN with ZSJ-0228 dosed at L1 resulted in the resolution of proteinuria in 14% of the mice. Mice treated with ZSJ-0228 dosed at L2 and L3 levels resulted in the resolution of proteinuria in ∼60% of the mice in both groups. Treatment with ZSJ-0228 dosed at L4 resulted in the resolution of proteinuria in 30% of the mice. The reduction and/or resolution of the proteinuria, improvement in renal histological scores, and survival data indicate that the most effective dose range for ZSJ-0228 in treating LN in NZB/W F1 mice is between 1.0 and 3.0 mg/kg/day Dex equivalent. Typical GC-associated side effects (e.g., osteopenia, adrenal glands atrophy, etc.) were not observed in any of the ZSJ-0228 treatment groups, confirming its excellent safety profile.

IgA-dominant infection-associated glomerulonephritis in the pediatric population.

IgA-dominant infection-associated glomerulonephritis is well-documented in adults but has not been studied in depth in children. We assessed the incidence of pediatric IgA-dominant infection-associated glomerulonephritis and clinical and kidney biopsy findings. Pediatric native kidney biopsies over a 10-year period with IgA dominance, strong C3, and findings indicative of infection-associated etiology were identified. We identified 9 cases of IgA-dominant infection-associated glomerulonephritis, 0.8% of pediatric native kidney biopsies. Seven patients presented with elevated creatinine. All had hematuria and proteinuria. Eight patients had clinical evidence of infection: one each with central port infection by methicillin-sensitive Staphylococcus aureus, recurrent streptococcalpharyngitis and recent otitis media, streptococcalpharyngitis demonstrated 8months after biopsy, suspected streptococcalscalded skin syndrome, and viral gastroenteritis, and three with serologic evidence of Streptococcal infection but no identified site of infection. All but one patient experienced short-term normalization of creatinine and resolution of proteinuria, though two eventually progressed to kidney failure: one 3years later due to progressive disease and one 11years later due to focal segmental glomerulosclerosis without concurrent immune deposits. Pediatric IgA-dominant infection-associated glomerulonephritis is rare, and generally has a favorable prognosis, contrasting that seen in adults with severe comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary.

Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.

Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.

Podocytopathies.

Podocytopathies are kidney diseases in which direct or indirect podocyte injury drives proteinuria or nephrotic syndrome. In children and young adults, genetic variants in >50podocyte-expressed genes, syndromal non-podocyte-specific genes and phenocopies with other underlying genetic abnormalities cause podocytopathies associated with steroid-resistant nephrotic syndrome or severe proteinuria. A variety of genetic variants likely contribute to disease development. Among genes with non-Mendelian inheritance, variants in APOL1 have the largest effect size. In addition to genetic variants, environmental triggers such as immune-related, infection-related, toxic and haemodynamic factors and obesity are also important causes of podocyte injury and frequently combine to cause various degrees of proteinuria in children and adults. Typical manifestations on kidney biopsy are minimal change lesions and focal segmental glomerulosclerosis lesions. Standard treatment for primary podocytopathies manifesting with focal segmental glomerulosclerosis lesions includes glucocorticoids and other immunosuppressive drugs; individuals not responding with a resolution of proteinuria have a poor renal prognosis. Renin-angiotensin system antagonists help to control proteinuria and slow the progression of fibrosis. Symptomatic management may include the use of diuretics, statins, infection prophylaxis and anticoagulation. This Primer discusses a shift in paradigm from patient stratification based on kidney biopsy findings towardspersonalized management based on clinical, morphological and genetic data as well as pathophysiological understanding.

P0384PROTEINURIA SELECTIVITY INDEX MAY PREDICT RITUXIMAB RESPONSE IN MCD AND FSGS

Abstract Background and Aims Proteinuria selectivity index (PSI) predicts steroid responsiveness in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Rituximab, a monoclonal antibody targeting CD20, has increasingly recognized as a potential therapy of idiopathic podocytopathies, such as MCD and FSGS, although the mechanism of action is still unrecognized and randomized controlled studies are still lacking. Currently, no tools are available to predict responsiveness to RTX. We explored the role of PSI as a potential predictor of RTX responsiveness in MCD and FSGS. Method We analysed cases of biopsy-proven MCD and FSGS followed at one single centre, who received RTX therapy. Baseline data, including proteinuria and PSI, were collected. Proteinuria was considered selective with PSI (clearance of urinary IgG/transferrin ratio) <0.20. Complete remission (CR) was resolution of proteinuria and clinical symptoms, while partial remission (PR) was proteinuria decrease (>50%) and substantial improvement of clinical symptoms. Results RTX was administered to 14 patients with MCD and 16 patients with FSGS and, of them, PSI was available before treatment for 10 and 14 patients, respectively. Baseline characteristics of the patients are shown in Table 1. Among the 24 cases with available PSI, CR was reported in 12 and PR in 5, while 9 did not respond to RTX. All patients who achieved CR and PR had selective proteinuria at baseline, while all patients with PSI >0.20 did not respond to RTX (Figure 2). Median relapse-free survival was 25.4 months. Among responders, in 10 out of 19 patients (53%) the relapse occurred between 4 and 60 months from initial treatment. No potentially life-threatening adverse events have been observed. Conclusion Selective proteinuria before treatment can predict the response to RTX in adult patients with steroid-dependent and refractory forms of MCD and FSGS.

P24 The successful use of anakinra to control protracted immune reconstitution inflammatory syndrome in HIV associated tuberculosis: a report of two cases

Abstract Background Paradoxical inflammatory reactions are well known to complicate tuberculosis (TB) and are observed with greater frequency in patients who are co-infected with HIV. Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical inflammatory reaction following early immune system recovery after initiation of antiretroviral therapy. IRIS complicates one in five cases of HIV-associated TB. Most cases of IRIS respond to short courses of corticosteroids; however, morbidity and mortality is increased in central nervous system TB or with protracted reactions. There are no evidence-based treatment guidelines but montelukast, thalidomide and anti-tumour necrosis factor agents have been used to treat protracted paradoxical TB IRIS. Interleukin-1 mediated inflammation has been implicated in TB IRIS. We describe two cases using anakinra (recombinant human interleukin-1 receptor inhibitor) to control protracted, life-threatening inflammation in HIV associated TB. Methods The cases are presented in the results section. Results Case 1: A 33-year-old female from Ethiopia presented with sub-acute onset of fever, malaise with massive abdominal and thoracic lymphadenopathy. She was diagnosed with HIV (CD4=60 cells/mm3) and fully sensitive TB from lymph node aspirate. Despite two courses of TB treatment she developed a 3-year protracted IRIS with fevers, malaise and multiple cold abscesses and was unable to wean below 20mg prednisolone. AA amyloidosis developed with nephrotic range proteinuria and renal amyloid deposition on biopsy. Inflammation failed to respond to montelukast or colchicine, prompting anakinra initiation (100mg daily) with rapid clinical response, resolution of proteinuria, normalisation of inflammatory markers and successful weaning of corticosteroids. She is maintained on 100mg alternate-daily anakinra having failed an attempt to withdraw the treatment at seven years. Case 2: A 41-year-old Zimbabwean teacher with HIV (stable on antiretroviral therapy, complete viral suppression, CD4=245 cells/mm3) presented with one month of fever, weight-loss and headache with no neurological deficit. He was diagnosed with isoniazid mono-resistant miliary TB with tuberculomata in his medulla, pons and both cerebral hemispheres on magnetic resonance imaging (MRI). Following initiation of TB treatment, he developed worsening headaches, left sided weakness and dysphasia with increasing size and surrounding oedema of his tuberculomata on brain MRI. Brain biopsy demonstrated necrotic granulomatous inflammation with visible acid-fast bacilli but no mycobacterial growth, compatible with paradoxical inflammation. He required protracted and high dose dexamethasone. After 18 months without successfully weaning steroids, with cognitive and functional impairment and unstable tuberculomata on serial brain MRI, anakinra was initiated with significant clinical, functional and radiological improvement. He is maintained steroid-free on 100mg alternate-daily anakinra at four years. Conclusion This is the first published report using anakinra to control severe and life-threatening protracted paradoxical inflammation and reduce steroid exposure in HIV-associated tuberculosis. Disclosures A.J. Keeley None. V. Parkash None. A. Tunbridge None. J. Greig None. P. Collini None. R.S. Tattersall None.

The Promise of Single Kidney Transplants from Small Pediatric Donors

The Promise of Single Kidney Transplants from Small Pediatric Donors

Favorable Renal Outcome of Japanese Children with Severe IgA Nephropathy With Nephrotic Syndrome

Nephrotic syndrome is a rare but severe feature of IgA nephropathy. Nine Japanese children with severe IgA nephropathy with nephrotic syndrome. All received low-dose intravenous methylprednisolone (IVMP) within five weeks after the disease onset. Eight out of nine patients achieved resolution of proteinuria without severe adverse events. Early low-dose intravenous methylprednisolone may be safe and effective for children with severe IgA nephropathy with nephrotic syndrome.

Effect of complete or partial proteinuria recovery on long-term outcomes of lupus nephritis.

We aimed to evaluate the effect of complete recovery (CR), partial recovery (PR), and no recovery (NR) of proteinuria at 2 years from the diagnosis of LN on long-term renal and extra-renal outcomes. Patients with LN and proteinuria attending the Lupus Center from 1970 to 2015 were analyzed. At 2 years from diagnosis of LN, patients were divided into three groups (CR, PR, and NR), and long-term outcomes were studied up to 15 years or last visit available. CR was defined as resolution of proteinuria, PR as a reduction ≥50% in baseline proteinuria, and NR as a reduction <50% compared to baseline. Long-term outcomes examined included renal outcomes [low eGFR, ESRD, and composite renal (low eGFR, ESRD, and dialysis/transplant)], cardiovascular outcomes, damage, and death. Kaplan-Meier plots, time-independent and time-dependent Cox proportional hazards models were applied to examine the effect of CR, PR, or NR on long-term outcomes. Of 277 patients, 71.8% achieved CR, 18.4% PR, and 9.8% NR at 2 years. CR compared to NR and CR compared to PR were protective against low eGFR and composite renal outcome in time-independent and time-dependent analyses. CR compared to PR protected against damage in the time-independent analysis. Overall, the comparison of CR and PR favored CR for long-term renal outcomes. CR at 2 years from diagnosis of LN protected against renal outcomes (low eGFR, ESRD/dialysis, and transplant). CR is more favorable compared to PR and clinicians should aim for CR to improve long-term outcomes in LN.

Resolution of Liver Cirrhosis After Cardiac Transplantation in a Patient With a Fontan Circulation

Purpose: Liver fibrosis is inevitable over time with a Fontan circulation. However, it no longer contraindicates heart transplantation in this cohort, with similar survival post-transplant in presence of cirrhosis [[1]Simpson K. Esmaeeli A. Khanna G. et al.Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function.J Heart Lung Transplant. 2014; 33: 170-177Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar]. We discuss a case demonstrating reversal of liver cirrhosis post-transplantation in a patient with a Fontan circulation. Methodology: Serial liver testing via transient elastography (Fibroscan) and pathology before and after heart transplantation was performed in a 28-year-old male with failing Fontan physiology. Renal function was also assessed. Results: The subject was born with double inlet left ventricle, pulmonary stenosis and situs inversus. He developed Fontan failure 18 years after initial atrio-pulmonary Fontan surgery, and had persistent NYHA class III symptoms despite Fontan conversion surgery. Pre-transplant Fibroscan suggested frank cirrhosis with median liver stiffness of 44 kPa (normal < 7 kPa), ultrasound demonstrated evidence of portal hypertension, elevated liver enzymes (GGT 136, ALT 54) and thrombocytopaenia due to hypersplenism. He had moderate renal impairment with significant proteinuria. After successful orthotopic cardiac transplant, there was marked reduction in liver stiffness to 11 kPa. Repeat ultrasound showed normal portal vascular size with reduced splenomegaly. Liver and renal function as well as platelet count have normalised, with resolution of proteinuria. Conclusion: Cardiac cirrhosis in a Fontan circulation is reversible with normalisation of physiology after cardiac transplantation.

A case report of unusually long lag time between immunotactoid glomerulopathy (itg) diagnosis and diffuse large B-cell lymphoma (DLBCL) development.

BackgroundImmunotactoid glomerulopathy (ITG) is a rare cause of proteinuria characterized by organized microtubular deposits in the glomerulus. ITG has been associated with underlying lymphoproliferative disorders and any renal impairment may be reversible with treatment of the concomitant hematologic malignancy. This case is the first reported in literature where diffuse large B cell lymphoma developed two years following the initial ITG diagnosis.Case presentationA 55-year-old woman with a history of well-controlled diabetes mellitus and thalassemia trait presented with proteinuria (830 mg/day) in 2010. Initially, she was managed with renin-angiotensin-aldosterone-system blockade. In 2012, the proteinuria worsened (4.3 g/day) and a renal biopsy showed immunotactoid glomerulopathy (Fig. 1). Despite extensive work up, no lymphoproliferative disorder was initially found. In January 2014, the patient presented with a soft-palate mass found on biopsy to be diffuse large B-cell lymphoma. She received 6 cycles of R-CHOP, 4 cycles of high dose methotrexate chemotherapy for CNS prophylaxis and 30 Gy of Intensity Modulated Radiation Therapy. Follow-up revealed complete remission of diffuse large B-cell lymphoma and resolution of proteinuria from the ITG.ConclusionAs we recognize that patients with ITG may develop hematopoietic neoplasms, close long-term monitoring is important. Moreover, treatment of the lymphoproliferative disorder can allow for complete remission of ITG.

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS.

Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of favorable response to rituximab could be identified. Twenty-two consecutive patients with FSGS (median age =14.4 years old; range =6.2-25.0 years old) and age of onset of nephrotic syndrome 1-18 years old receiving rituximab for clinical indications between October of 2009 and February of 2014 were studied. Indications for rituximab were lack of sustained remission despite calcineurin inhibitors (CNIs) and mycophenolate in steroid-resistant patients and lack of steroid-sparing effect with cyclophosphamide and CNI or CNI toxicity in steroid-dependent patients. Exclusion criteria were infantile onset, known genetic mutations, and secondary causes. Rituximab (375 mg/m(2)) was given fortnightly up to a maximum of four doses. Immunologic subset monitoring was performed at baseline and regular intervals until relapse. Median follow-up duration postrituximab was 26.7 months (range =6.5-66.5 months). Baseline immunologic subsets were examined for association with rituximab response defined as resolution of proteinuria with discontinuation of prednisolone and CNI 3 months postrituximab. Twelve patients (54.5%) responded to rituximab. Mitogen-stimulated CD154(+)CD4(+)CD3(+) subset before rituximab was significantly lower in FSGS responders compared with nonresponders (54.9%±28.1% versus 78.9%±16.4%; P=0.03). IFN-γ(+)CD3(+) and IL-2(+)CD3(+) were similarly decreased in responders compared with nonresponders (0.6%±0.8% versus 7.5%±6.1%; P=0.003 and 0.2%±0.5% versus 4.0%±4.7%; P<0.01, respectively). Recovery of all three activation subsets occurred 6 months postrituximab treatment (CD154(+)CD4(+)CD3(+), 74.8%±17.2%; IFN-γ(+)CD3(+), 7.1%±7.7%; and IL-2(+)CD3(+), 7.9%±10.9%; P<0.01). Receiver-operating characteristic analysis using optimal cutoff values showed that activated CD154(+)CD4(+)CD3(+) <83.3% (area under the curve [AUC], 0.81; 95% confidence interval [95% CI], 0.61 to 1.00), IFN-γ(+)CD3(+)<2.5% (AUC, 0.90; 95% CI, 0.75 to 1.00), and IL-2(+)CD3(+)<0.3% (AUC, 0.78; 95% CI, 0.57 to 0.98) were good predictors of rituximab response. We have identified prognostic markers that define a subset of patients with FSGS bearing an immunologic signature representing hyporesponsiveness to T cell stimulation and therefore, who respond better to rituximab.

Successful Treatment of Focal Segmental Glomerulosclerosis after Kidney Transplantation with Plasma Exchange and Abatacept in a Patient with Juvenile Rheumatoid Arthritis.

Recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation is difficult to treat. Recently a series of four patients unresponsive to plasma exchange (PE) and rituximab, who were successfully treated with abatacept, has been reported. We present a 26-year-old Caucasian patient who suffered from juvenile rheumatoid arthritis and developed severe proteinuria eleven days after transplantation. An allograft biopsy was suggestive of recurrent focal segmental glomerulosclerosis. He did not respond to PE therapy. A first dose of abatacept produced partial remission. Four weeks later proteinuria again increased and a second biopsy showed progression of disease. After another ineffective course of PE he was given a second dose of abatacept, which was followed by rapid, complete, and sustained resolution of proteinuria. This treatment caused a significant increase in BK and JC viremia. Whether abatacept ameliorated proteinuria via an effect on podocytes or on the patient's primary disease remains speculative.

Absence of Mesangial C1q Deposition Is Associated with Resolution of Proteinuria and Hematuria after Tonsillectomy Plus Steroid Pulse Therapy for Immunoglobulin A Nephropathy

Introduction and Aims: Deposition of C1q occurs in 0 to 45% of patients with IgAN. In order to identify whether mesangial C1q deposition in IgAN is a novel marker for the response to tonsillectomy plus steroid pulse therapy (TSP), we studied the association between mesangial C1q deposition in IgAN and the remission rate after TSP therapy for IgAN. Methods: We conducted a retrospective cohort study at a single Japanese center. We analyzed data on 110 patients diagnosed with IgA nephropathy who received TSP between January 2003 and December 2012. Positive C1q findings were defined as diffuse mesangial C1q deposition. The study outcome was the resolution of abnormal urinary findings and was defined as negative proteinuria and negative occult blood 1 year after steroid pulse therapy. Results: In all enrolled cases, 69 patients (62.7%) went into remission. Ten out of 24 (41.7%) C1q-positive patients experienced remission, and 59 out of 86 (68.6%) C1q-negative patients experienced remission. Multiple logistic regression model analysis showed that the absence of C1q deposition increased the odds ratio for remission (odds ratio 4.41; 95% confidence interval 1.33-15.75, p = 0.017). Conclusions: These results suggest that the absence of diffuse C1q deposition in the mesangial area of the glomerulus in patients with IgA nephropathy is a positive predictive sign for a response to TSP and is associated with the resolution of urinary abnormalities 1 year after TSP.

C1q nephropathy in the setting of granulomatosis with polyangiitis treated with tacrolimus.

C1q nephropathy in the setting of granulomatosis with polyangiitis treated with tacrolimus.

Aldosterone antagonists for preventing the progression of chronic kidney disease.

Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a review first published in 2009. To evaluate the effect of aldosterone antagonists (both selective (eplerenone) and non-selective (spironolactone)) alone or in combination with ACEi or ARB in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including major cardiovascular events, hospitalisation and all-cause mortality; kidney function (proteinuria, glomerular filtration rate (GFR), serum creatinine, and need for renal replacement therapy; and adverse events (including gynaecomastia and hyperkalaemia). For this update, we searched the Cochrane Renal Group's Specialised Register to 30 January 2013 using search terms relevant to this review. We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists alone or in combination with ACEi or ARB (or both) with other anti-hypertensive strategies or placebo. Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We tested for heterogeneity in estimated treatment effects using the Cochran Q test and I² statistic. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals (CI) and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used. We identified 27 studies (1549 participants) that were eligible for inclusion. These studies provided no data relating to aldosterone antagonists in addition to ACEi or ARB (or both) on patient-level outcomes including major cardiovascular events and mortality and progression to end-stage kidney disease (ESKD) requiring dialysis or transplantation.Compared with ACEi or ARB (or both), non-selective aldosterone antagonists (spironolactone) combined with ACEi or ARB (or both) significantly reduced 24-hour protein excretion (11 studies, 596 participants): SMD -0.61, 95% CI -1.08 to -0.13). There was a significant reduction in both systolic and diastolic blood pressure (BP) at the end of treatment with additional non-selective aldosterone antagonist therapy (systolic BP (10 studies, 556 participants): MD -3.44 mm Hg, 95% CI -5.05 to -1.83) (diastolic BP (9 studies, 520 participants): MD -1.73 mm Hg, 95% CI -2.83 to -0.62).However, we found that aldosterone antagonist treatment had imprecise effects at the end of treatment on GFR (9 studies, 528 participants; MD -2.55 mL/min/1.73 m², 95% CI -5.67 to 0.51), doubled the risk of hyperkalaemia (11 studies, 632 patients): RR 2.00, 95% CI 1.25 to 3.20; number needed to treat for an additional harmful outcome (NNTH): 7.2, 95% CI 3.4 to ∞) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (4 studies, 281 patients): RR 5.14, 95% CI 1.14 to 23.23; NNTH: 14.1, 95% CI 8.7 to 37.3).Most studies enrolled few patients (range 12 to 268) and were powered to observe differences in surrogate end points rather than patient-focused outcomes. Nine studies had a cross-over design and the majority of studies did not adequately report study methods to assess methods and study quality. Aldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown.