Rationale for the evaluation of renal functional reserve in allogeneic stem cell transplantation candidates: a pilot study.

Background: The main purpose of our study was to evaluate the ability of renal functional reserve (RFR) to stratify the risk of acute kidney injury (AKI) occurrence within 100 days of hematopoietic stem cell transplantation (HSCT) and to predict any functional recovery or the onset of chronic kidney disease. A secondary aim was to identify the clinical/laboratory risk factors for the occurrence of AKI. Methods: The study design is prospective observational. We enrolled 48 patients with normal basal glomerular filtration rate (bGFR) who underwent allogenic HSCT. A multiparameter assessment and the Renal Functional Reserve Test (RFR-T) using an oral protein load stress test were performed 15 days before the HSCT. Results: Different RFRs corresponded to the same bGFR values. Of 48 patients, 29 (60%) developed AKI. Comparing the AKI group with the group that did not develop AKI, no statistically significant difference emerged in any characteristic related to demographic, clinical or multiparameter assessment variables except for the estimated GFR (eGFR). eGFR ≤100 mL/min/1.73 m2 was significantly related to the risk of developing AKI (Fisher's exact test, P = .001). Moreover, RFR-T was lower in AKI+ patients vs AKI- patients, but did not allow statistical significance (28% vs 40%). In AKI patients, RFR >20% was associated with complete functional recovery (one-sided Fisher's exact test, P = .041). The risk of failure to recover increases significantly when RFR ≤20% (odds ratio = 5.50, 95% confidence interval = 1.06-28.4). Conclusion: RFR identifies subclinical functional deterioration conditions essential for post-AKI recovery. In our cohort of patients with no kidney disease (NKD), the degree of pre-HSCT eGFR is associated with AKI risk, and a reduction in pre-HSCT RFR above a threshold of 20% is related to complete renal functional recovery post-AKI. Identifying eGFR first and RFR second could help select patients who might benefit from changes in transplant management or early nephrological assessment.

[The genetic basis of post-bone marrow transplant thrombotic microangiopathy: is this the last piece of the puzzle?]

Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplantation (HSCT) associated with kidney injury and significant mortality. Recent studies indicate that dysregulation of the alternate complement pathway may be at the basis of the development of TA-TMA. Currently, there are no pre-transplant screening tools to identify patients at risk. To explore the mechanism of TA-TMA, we performed a genetic study that allowed us to identify the deletion of the CFHR3-CFHR1 region in homozygosity. We report the clinical case of a 47-year-old woman who underwent haploidentical HSCT complicated by TA-TMA confirmed by renal biopsy. The patient discontinued treatment with calcineurin inhibitors (potential inducers of TA-TMA) with a brief introduction of prednisone until complete resolution of renal damage and microangiopathy. Identifying genetic variants that affect the mechanism of the alternate complement pathway could help in the stratification of the risk of TA-TMA and in implementing a personalized therapeutic approach.

[Membranous nephropathy secondary to rheumatoid arthritis occurring during anti-TNFalpha therapy and responsive to second-line treatment with rituximab]. / Nefropatia membranosa secondaria ad artrite reumatoide esordita durante la terapia con anti-TNFalpha e responsiva al trattamento di seconda linea con rituximab.

We report the case of a patient with rheumatoid arthritis (RA) who developed a membranous nephropathy (MN) with nephrotic syndrome while receiving etanercept, a fusion protein that binds specifically to TNFalpha and blocks its interaction with TNFalpha receptors. A 62-year-old man with RA treated with etanercept was admitted to our unit in March 2008 because of a full-blown nephrotic syndrome. Renal biopsy showed a typical MN. Since no improvement of proteinuria was observed after withdrawal of etanercept, we administered rituximab (1 g two weeks apart repeated after 6 months). The signs and symptoms of RA improved and proteinuria decreased from 7.2 g/24h to 2.3 g/24h. MN is an immunological glomerulonephritis that may complicate other immune-mediated diseases or may be triggered by a number of drugs. The clinical improvement of both RA and MN after rituximab may indirectly confirm the role of antibodies in the pathogenesis of these diseases, although the mechanisms of action of this drug in immunological disorders remain to be elucidated.