Sofia Santos

Monoclonal gammopathy of renal significance: Diagnostic workup

The clinical spectrum of diseases associated with monoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always available, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic difficulties of these entities.

Correlations between donor-specific antibodies and non-adherence with chronic active antibody-mediated rejection phenotypes and their impact on kidney graft survival

Chronic-active antibody-mediated rejection (CAABMR) is associated with poor kidney graft survival and has no clear effective treatment. Forty-one cases of CAABMR were detected in indication graft biopsies and evaluated according to current Banff classification. We investigated the impact of concurrent donor-specific antibodies (DSA) and their characteristics, together with non-adherence regarding immunosuppression on CAABMR histopathological phenotypes and prognosis. Twenty-four (59%) patients had detectable DSA at biopsy, with 15 of them being considered non-adherent. Graft function at biopsy was similar in DSA (+) and (-) patients. DSA (+) patients had significantly higher tubulointerstitial inflammation (i and ti) and acute humoral (g+ptc+v+C4d) composite score than DSA (-). DSA (+)/non-adherent cases presented additionally with increased microvascular inflammation (ptc and v), besides having a distinctively lower ah score. C1q DSA strength was higher (P = .046) in non-adherent patients and correlated closely with C4d score (P = .002). Lower graft function and ah score, higher proteinuria and ci + ct score, and, separately per each model, DSA (+) (HR = 2.446, P = .034), DSA (+)/non-adherent (HR = 3.657, P = .005) and DSA (+)/C1q (+) (HR = 4.831, P = .003) status were independent predictors of graft failure. CAABMR with concomitant DSA pose a higher risk of graft failure. Adherence should be evaluated, and histopathological phenotyping and DSA characterization may add critical information.

Acute tubulointersticial nephritis with uveitis: A report of two cases

Tubulointersticial nephritis and uveitis syndrome is an idiopathic and rare cause of acute kidney injury that should not overlooked, because it usually requires specific therapeutic interventions. We report two distinct cases: a young and an elder female. Both cases presented with unspecific constitutional symptoms but had different onset of renal and ocular involvement. Both were treated with topical and systemic corticoids and although there was a good initial response in both cases, an early relapse after steroids taper was observed in the younger patient and a persistent renal dysfunction in the older one. A high clinical suspicion and understanding of this disease is necessary for an adequate management and treatment of these patients. Recent data associates a worse renal prognosis when the disease appears in advanced age. In both of our cases the outcome was good but we had a short follow-up. The histological presentation of this disease in our older patient was similar to that reported in the literature, with a high percentage of fibrosis and chronicity of renal tissue that can contribute to the higher grade of renal dysfunction in this type of patients.

Original articleIncrease of allosensitization after a kidney graft failure: Predictors and effect on retransplantation outcomesAumento de la alosensibilización después de un fallo del injerto renal: predictores y efecto en los resultados del retrasplante

Patients who are candidates for a second kidney transplant (SKT) frequently have a higher level of panel reactive antibodies (PRA). We assessed the allosensitisation change after a first graft failure (GF), its predictors and impact on retransplantat outcomes. We retrospectively selected 140 adult patients who received a SKT. Recipient and donor characteristics were analyzed. We defined the delta PRA (dPRA) as the difference between peak PRA before the SKT and first one (cohort median value=+10%). Logistic regression analysis was used to determine risk factors for dPRA≥10% and acute rejection (AR) in the SKT. Univariable and multivariable Cox analysis was applied to assess independent predictors of second GF. Risk factors for dPRA≥10% at SKT were AR (OR=2.57; P=0.022), first graft survival <1 year (OR=2.47; P=0.030) and ABDR HLA mismatch (OR=1.38 per each mismatch; P=0.038). AR in the SKT was associated with dPRA≥10% (OR=2.79; P=0.047). Induction with a lymphocyte-depleting agent had a protective effect (OR=0.23; P=0.010). SKT survival was lower (P=0.008) in patients with a dPRA≥10% (75.6%, 60.5% in dPRA≥10%; 88.6%, 88.6% in dPRA<10% patients at 5 and 10 years, post-transplant respectively). Multivariable Cox regression showed that dPRA≥10% (HR=2.38, P=0.042), delayed graft function (HR=2.82, P=0.006) and AR (HR=3.30, P=0.001) in the SKT were independent predictors of retransplant failure. This study shows that an increased allosensitisation at retransplant was associated with the degree of HLA mismatch and led to poorer outcomes. De-emphasis of HLA matching in current allocation policies may be undesirable, particularly in patients with a higher chance of needing a SKT.Patients who are candidates for a second kidney transplant (SKT) frequently have a higher level of panel reactive antibodies (PRA). We assessed the allosensitisation change after a first graft failure (GF), its predictors and impact on retransplantat outcomes. We retrospectively selected 140 adult patients who received a SKT. Recipient and donor characteristics were analyzed. We defined the delta PRA (dPRA) as the difference between peak PRA before the SKT and first one (cohort median value = +10%). Logistic regression analysis was used to determine risk factors for dPRA ≥ 10% and acute rejection (AR) in the SKT. Univariable and multivariable Cox analysis was applied to assess independent predictors of second GF. Risk factors for dPRA ≥ 10% at SKT were AR (OR = 2.57; P = 0.022), first graft survival <1 year (OR = 2.47; P = 0.030) and ABDR HLA mismatch (OR = 1.38 per each mismatch; P = 0.038). AR in the SKT was associated with dPRA ≥ 10% (OR = 2.79; P = 0.047). Induction with a lymphocyte-depleting agent had a protective effect (OR = 0.23; P = 0.010). SKT survival was lower (P = 0.008) in patients with a dPRA ≥ 10% (75.6%, 60.5% in dPRA ≥ 10%; 88.6%, 88.6% in dPRA < 10% patients at 5 and 10 years, post-transplant respectively). Multivariable Cox regression showed that dPRA ≥ 10% (HR = 2.38, P = 0.042), delayed graft function (HR = 2.82, P = 0.006) and AR (HR = 3.30, P = 0.001) in the SKT were independent predictors of retransplant failure. This study shows that an increased allosensitisation at retransplant was associated with the degree of HLA mismatch and led to poorer outcomes. De-emphasis of HLA matching in current allocation policies may be undesirable, particularly in patients with a higher chance of needing a SKT.

Plasmapheresis in the Management of Acute Pancreatitis due to Severe Hypertriglyceridemia—Reporting New Cases

Acute pancreatitis is a potentially life-threatening disease. If the diagnosis and the treatment are not prompt, it can rapidly evolve to a medical emergency. Severe hypertriglyceridemia, defined as above 1000 mg/dl, is the third most common cause of acute pancreatitis. Conventional management includes fat dietary restriction and pharmacological treatment; however, these measures take time to be effective. Plasmapheresis seems to be an alternative and safe adjunctive therapy because it allows the rapid reduction of the trigger agent in circulation. Its use, especially in severe cases, has been increasingly reported. The authors report three cases of severe hypertriglyceridemia-induced pancreatitis in which early plasmapheresis was successfully used with other supportive clinical management.