Extracapillary proliferation is an independent predictive factor in Immunoglobulin A nephropathy.

BACKGROUND: Oxford classification of Immunoglobulin A Nephropathy (IgAN) identifies four pathological features as predictors of renal outcome (MEST-score): mesangial proliferation (M); endocapillary proliferation (E); segmental glomerulosclerosis (S); tubular atrophy/interstitial fibrosis (T). In particular extracapillary proliferation (Ex) was not considered as an independent histological variable predicting renal outcome. Recently the VALIGA study provided a validation of the Oxford classification in a large European cohort of IgAN patients and re-stated that Ex is not associated with a worse renal prognosis. We propose a retrospective study to evaluate the predictive value of the MEST-score in a multi-centre, single region group of patients from central Italy and in addition, to investigate Ex as a marker predicting renal outcome. METHODS: One hundred and seven patients were enrolled in this study. Clinical data of each patient were available at diagnosis and follow-up. The median age at diagnosis was 36.7 years; 72% of the patients were males. Histological parameters were those included in the MEST-score of the Oxford classification; in addition, Ex was also assessed. RESULTS: Multiple linear regression models for survey were used. Statistical analysis showed a correlation between the progression of renal decline, in terms of estimated glomerular filtration rate (slope eGFR), and M, S, T. Differently from Oxford and VALIGA studies, no correlation was found with E, while Ex correlated with a decline of eGFR. CONCLUSIONS: Our results suggest that Ex represents an additional independent variable associated with a faster decline of renal function in IgAN.

Renal involvement in Waldenström's macroglobulinemia: case report and review of literature.

Waldenström's macroglobulinemia (WM) is a rare lymphoid neoplasia, accounting for 2% of all hematological malignancies. Renal complications occur rather rarely compared to multiple myeloma. The most common renal manifestations are mild proteinuria and microhematuria. We describe a case of MW presenting with acute renal failure and NS. A 67-year-old man was referred to our hospital for sudden onset nephrotic syndrome. Electrophoresis revealed a monoclonal component in the gamma region, which was classified as an IgM k. During hospitalization, acute kidney injury developed, with creatinine up to 5 mg/dL, despite adequate hydration and alkalinization. A kidney biopsy was performed, showing minimal change disease (MCD) with interstitial and capsular lymphoid infiltrates of B-Lymphocytes CD20+. B-lymphocytes infiltration suggested the possibility of renal localization of lymphoproliferative disorder. So, bone marrow histology was performed, revealing lymphoplasmacytic lymphoma (WM). The patient was treated with bortezomib, desamethasone, and rituximab, with partial recovery of renal function (creatinine 1.5 mg/dL) and complete remission of proteinuria after 8-month follow-up. The remission of NS in our patient with rituximab seems to emphasize the pathogenetic role of B cells in MCD, although a coincident effect of immunosuppression on both the underlying renal disease and the hematologic disease cannot be excluded.

Fludarabine in chronic lymphocytic leukemia with membranous nephropathy.

Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Western countries. Despite its relative frequency, the association of glomerular disease is extremely rare. We present a case of membranous nephropathy (MN) during CLL treated with fludarabine. A 74-year-old man was admitted to our hospital because of the onset of nephrotic syndrome (proteinuria was 7 g/24 h). Six years before, he had been diagnosed with CLL. Biochemical analysis showed the following results: creatinine was 1.7 mg/dL (creatinine clearance was 39 mL/min), urea was 64 mg/dL, hemoglobin was 8.6 g/dL, and white blood cells was 16,580/mm(3) (60% lymphocytes). The urine sediment revealed 7-8 red blood cells and many hyaline and granular casts. No monoclonal peak was demonstrated in either serum or urine electrophoresis. Bence-Jones proteinuria was negative. The patient underwent renal biopsy that showed MN with an extensive lymphocyte perivascular infiltration; immunohistochemistry on renal biopsy specimen showed that infiltrating lymphocytes were CD20+. Moreover, DNA from tissue fractions was analyzed by qualitative polymerase chain reaction-based detection of clonal gene rearrangements of the immunoglobulin heavy chain gene, confirming the monoclonality of the infiltrating lymphocytes. The patient was started on fludarabine as monotherapy, with complete remission of proteinuria and recovery of renal function (creatinine clearance was 75 mL/min) after 1 year of follow-up.

[New therapeutic prospects for renal transplant: extracorporeal photochemotherapy]. / Nuove prospettive terapeutiche per il trapianto di rene: la fotochemioterapia extracorporea.

Since 1960, different classes of immunosuppressive drugs have been used in the post-transplant follow-up. Each is assessed for its effectiveness in preventing rejection but also on the basis of the many side effects induced by prolonged treatment. To reduce these side effects, continuous development of knowledge and medical technology to create cutting-edge therapies in the field is necessary. One of these is extracorporeal photochemotherapy (ECP), an immunomodulatory therapy approved by the United States Food and Drug Administration in 1988 for the treatment of advanced forms of cutaneous T-cell lymphoma. EC P is a useful therapeutic tool for the development of immunomodulation supported by CD8+ clone-specific cytotoxic lymphocytes. The T cells targeted by EC P are modified by photoactivation and seem to develop marked immunogenicity with no suppression of the immune response. Recent studies suggest the possible utility of EC P in the treatment of glomerulonephritis and in countering rejection after transplantation of organs including the kidney.