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Introduction: Therapy of proliferative lupus nephritis (PLN) is yet to be optimized. Standard of care for induction consists of intravenous (IV) cyclophosphamide (CYC) and steroids, which shows an improved outcome, but end-stage renal disease (ESRD) progression, increased mortality, and therapy-related adverse effects remain a major concern. The other treatment reported to induce early remission was the multitarget therapy comprising tacrolimus, mycophenolate, and steroid, but infections were high in the multitarget therapy. Considering azathioprine as a potentially safer and effective alternative anti-B-cell therapy, modified multitarget therapy (MMTT) was planned replacing mycophenolate with azathioprine. Material and Methods: A single-center, 24-week, open-label, randomized controlled trial comprising adults of age 18-65 years with biopsy-proven PLN was carried out. The intervention groups were 1) MMTT: tacrolimus 0.075 mg/kg/day and azathioprine 2 mg/kg/day and 2) IV CYC group with a starting dose of 0.75 (adjusted to 0.5-1.0) g/m2 every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. Results: Among 100 randomized patients, 48 were in MMTT arm and 52 were in IV CYC arm. At the end of 24 weeks, overall remission (complete and partial) was comparable in both the arms: MMTT (86.36%) and IV CYC (87.75%). There was comparable proteinuria reduction and systemic lupus erythematosus disease activity index (SLEDAI) score improvement with recovery of complement level C3 in both groups. Major adverse events were numerically more in the IV CYC group, including one death from pneumonia. Conclusion: The MMTT arm is as effective as IV CYC in improving short-term outcome in PLN, with a comparable safety profile.
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Steroids have been the cornerstone of first-line therapy in adult-onset minimal change disease (MCD). The period of exposure to high dose steroids may be longer in adult MCD patients and would result in higher rates of steroid-related side effects. Although tacrolimus (TAC) is known to be effective in steroid-dependent/resistant MCD as well as in nephrotic syndrome due to other causes, there are minimal data available for assessing the effectiveness of TAC as the first-line agent in adult MCD. This is a prospective, open-label, randomized controlled study conducted from April 2014 to March 2016. Patients were randomized into two groups A and B which received TAC for 12 months and oral steroids for six months, respectively. Primary outcomes were remission rates, drug resistance was measured at 6, 12,and 18 months in each group and secondary outcomes were relapse rates, sustained remission rates, dependency, and adverse effects were measured at 18 months in both groups. At six months, total response (TR, i.e., complete and partial remission) was achieved in 80% in the TAC group and 78.26% in the steroid group (P = 1.000). At 12 months, TR was 60% in the TAC group and 43.48% in the steroid group (P = 0.386). At 18 months, TR rate was 44% in the TAC group and 43.48% in the steroid group (P = 1.000). About 32% in the TAC group and 39.13% in steroid group had relapsed by 18 months. Serious adverse effects were similar in the two groups, but overall adverse effects were more in the steroid group. TAC as a primary agent is not inferior to steroids in inducing remission. TAC may be considered as an alternative agent to steroid in high-risk groups such as elderly patients, uncontrolled diabetes and young females as a primary agent in the management of adult MCD.
Assuntos
Imunossupressores/uso terapêutico , Nefrose Lipoide/tratamento farmacológico , Tacrolimo/uso terapêutico , Adulto , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Nefrose Lipoide/fisiopatologia , Estudos Prospectivos , Recidiva , Esteroides/efeitos adversos , Esteroides/uso terapêutico , Tacrolimo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Renal allograft dysfunction (RAD) can have myriad causes and presentations. Allograft biopsy remains the gold standard for optimum management. This is a retrospective study carried out at a tertiary care institute from August 2011 to March 2016. Details of the renal allograft biopsy requisitions were recorded and analyzed. Two hundred and two patients had undergone kidney transplantation (KT) during the study period. One hundred and twenty-six had undergone renal biopsy for RAD. The acute asymptomatic rise of serum creatinine was the most common clinical presentation (47.61%) followed by chronic RAD (CRAD) (19.84%), proteinuria (15.87%), immediate graft dysfunction (10.31%), and persistent active urinary sediments (6.34%) in that order. The incidence of delayed graft function was 1.98%. The overall incidence of biopsy-proven rejection was 8.41% within oneyear and 8.91% beyond oneyear of transplant. Acute cellular rejection (ACR) [with or without antibody-mediated rejection (AMR)] was found in 65%; AMR was found in 40% and 15% had both ACR and AMR. Borderline acute cell-mediated rejection was found in 22.5% of biopsies. CRAD was due to chronic rejection and chronic calcineurin inhibitor toxicity in only about one-fourth of the cases. Incidence of glomerulo-nephritis was 10.89% and most of these occurred two years after KT. Renal allograft biopsy was associated with minor complications in 3.17% of cases. Clinical presentations do not reliably distinguish the various causes of RAD. Allograft biopsy is a mainstay in the diagnosis of RAD and is safe. Results of live donor first transplantation using complement-dependent cytotoxi-city crossmatch are comparable to those programs using newer methods like solid-phase assays. However, the direct comparison of these results with other studies may not be completely applicable.
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Rejeição de Enxerto , Transplante de Rim , Rim/patologia , Transplante Homólogo , Biópsia/estatística & dados numéricos , Creatinina/sangue , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Humanos , Índia/epidemiologia , Nefropatias/epidemiologia , Transplante de Rim/efeitos adversos , Transplante de Rim/estatística & dados numéricos , Complicações Pós-Operatórias , Estudos Retrospectivos , Centros de Atenção Terciária , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricosRESUMO
INTRODUCTION: Screening school children for urinary abnormalities is an inexpensive task but is not commonly undertaken in India. Although debated in western countries, its utility in early diagnosis of kidney disorders has been proved by studies from Asia. We examined the prevalence of asymptomatic urinary abnormalities (AUA), obesity, and hypertension in school children and analyzed data to identify potential risk factors among those detected with such abnormalities. METHODS: Children and adolescents 8 to 18 years of age of either gender, attending 14 public schools in West Bengal, were screened prospectively from July 2013 to July 2016 for detecting asymptomatic urinary abnormalities by a spot urine test using a dipstick. Sociodemographic profile, medical examination (weight, height, and blood pressure), and questionnaire-based data were recorded. RESULTS: A total of 11,000 children were screened. Of these, data from 9306 children were available for AUA, obesity, and hypertension. The prevalence rate was 7.44% (95% confidence interval [CI] = 6.91%-7.97%) for at least 1 AUA. Isolated hematuria was present in 5.2% (95% CI 4.75%-5.65%), whereas isolated proteinuria was present in 1.9% (95% CI = 1.62%-2.18%). The prevalence of prehypertension was 13.43% (95% CI = 12.74%-14.12%) and that of hypertension and abnormal body mass index was 4.05% (95% CI = 6.43%-7.47%) and 38.67 (95% CI = 37.68%-39.66%) respectively. DISCUSSION: The prevalence rates of AUA were comparable with those in some Asian countries but higher than in most developed countries. Of children and adolescents 8 to 18 years of age, those 13 to 18 years had significantly more high risk factors such as AUA, hypertension, and obesity.